|
1
|
Li W, Li A, Zhang X, Fei F, Gao X, Fang Y, Cao S, Yang H, Li W, Liu B. Transcriptomics reveals crowding stress inhibit the immune defense of the head kidney of the pearl gentian grouper juvenile through NF-κB signal pathway. DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY 2025; 162:105299. [PMID: 39645218 DOI: 10.1016/j.dci.2024.105299] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Revised: 11/24/2024] [Accepted: 12/04/2024] [Indexed: 12/09/2024]
Abstract
Crowding stress is a significant welfare factor affecting aquatic animals in recirculating aquaculture systems. Little is known regarding the influence of prolonged crowding stress on the immunity of juvenile pearl gentian groupers. However, research exploring the potential mechanisms through which crowding stress affects fish immune function is limited. Therefore, this study aims to investigate the effect of crowding stress on the immune stress of the pearl gentian grouper juvenile (♀Epinephelus fuscoguttatus × ♂ Epinephelus lanceolatus) under prolonged conditions. We focused on the pearl gentian grouper juvenile and selected low- and high-density groups as the experimental breeding densities. Research shows that crowding stress increases the activities of alkaline acid plum and acid phosphatase, reduces the activities of lysozyme and immunoglobulin M content. RNA sequencing and comparative transcriptomic analyses were employed to explore changes in the gene expression of juvenile pearl gentian groupers subjected to crowding stress. Differential gene expression analyses between the low- and high-density groups identified 5777 unigenes that were differentially expressed following crowding stress, with 3216 and 2561 upregulated and downregulated, respectively. In the GO and KEGG enrichment analyses, many of the enriched signaling pathways related to genes were associated with immunity and oxidative stress. In addition, the combined analyses of enzyme activity and transcriptomics indicated that crowding stress suppressed the immune function of juvenile pearl gentian groupers, reducing their immune ability. Overall, these findings offer new insights into the molecular mechanisms underlying crowding stress tolerance in juvenile pearl gentian grouper, suggesting that the NF-κB pathway plays a crucial role in the immune response of the head kidney of the pearl gentian grouper to long-term crowding stress.
Collapse
Affiliation(s)
- Wenyang Li
- State Key Laboratory of Mariculture Biobreeding and Sustainable Goods, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao, Shandong 266071, PR China
| | - Ao Li
- State Key Laboratory of Mariculture Biobreeding and Sustainable Goods, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao, Shandong 266071, PR China
| | - Xianhong Zhang
- State Key Laboratory of Mariculture Biobreeding and Sustainable Goods, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao, Shandong 266071, PR China
| | - Fan Fei
- State Key Laboratory of Mariculture Biobreeding and Sustainable Goods, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao, Shandong 266071, PR China
| | - Xiaoqiang Gao
- State Key Laboratory of Mariculture Biobreeding and Sustainable Goods, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao, Shandong 266071, PR China
| | - Yingying Fang
- State Key Laboratory of Mariculture Biobreeding and Sustainable Goods, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao, Shandong 266071, PR China
| | - Shuquan Cao
- State Key Laboratory of Mariculture Biobreeding and Sustainable Goods, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao, Shandong 266071, PR China
| | - Hongjun Yang
- Xingguang Marine Ranch Fishery Co., Ltd, Rizhao, 276800 PR China
| | - Wensheng Li
- Mingbo Aquatic Products Co., Ltd, Yantai, 261400 PR China
| | - Baoliang Liu
- State Key Laboratory of Mariculture Biobreeding and Sustainable Goods, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao, Shandong 266071, PR China; Mingbo Aquatic Products Co., Ltd, Yantai, 261400 PR China.
| |
Collapse
|
|
2
|
Kim JM, Lee HL, Go MJ, Kim HJ, Sung MJ, Heo HJ. Green Tea Attenuates the Particulate Matter (PM) 2.5-Exposed Gut-Brain Axis Dysfunction through Regulation of Intestinal Microenvironment and Hormonal Changes. J Microbiol Biotechnol 2024; 34:2492-2505. [PMID: 39572022 PMCID: PMC11729334 DOI: 10.4014/jmb.2409.09035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Revised: 10/15/2024] [Accepted: 10/19/2024] [Indexed: 12/31/2024]
Abstract
Chronic exposure to particulate matter (PM)2.5 causes brain damage through intestinal imbalance. This study was estimated to confirm the regulatory activity of green tea against chronic PM2.5 exposure-induced abnormal gut-brain axis (GBA) in BALB/c mice. The green tea, as an aqueous extract of matcha (EM), ameliorated the colon length, short chain fatty acid contents, antioxidant biomarkers, myeloperoxidase (MPO) activity, and serum inflammatory cytokines. EM regulated the gut microbiota related to tryptophan intake and hormone metabolism. EM showed regulatory effect of intestinal tight junction (TJ) protein, inflammatory response, and apoptotic biomarkers. In addition, EM improved PM2.5-induced tryptophan-related hormonal metabolic dysfunction in intestinal tissue and serum. Through the ameliorating effect on GBA function, the consumption of EM presented the protective effect against inflammatory effect, apoptosis, synaptic damage, and hormonal activity in cerebral tissue, and suppressed abnormal change of brain lipid metabolites. In particular, EM intake showed relatively excellent improvement effects on indicators including Bacteroides, Ruminococcus, Murinobaculaceae, Allopreyotella, cyclooxygenase-2 (COX-2), acetylcholinesterase (AChE), 11,12-dihydroxyeicosatrienoic acid (DHET), and intestinal acetate from the PM group. These findings indicate that the dietary intake of EM might provide a regulatory effect against PM2.5-exposed GBA dysfunction via the intestinal microbiota and hormonal changes.
Collapse
Affiliation(s)
- Jong Min Kim
- Division of Applied Life Science (BK21), Institute of Agriculture and Life Science, Gyeongsang National University, Jinju 52828, Republic of Korea
- Korea Food Research Institute, Wanju-gun 55365, Republic of Korea
| | - Hyo Lim Lee
- Division of Applied Life Science (BK21), Institute of Agriculture and Life Science, Gyeongsang National University, Jinju 52828, Republic of Korea
| | - Min Ji Go
- Division of Applied Life Science (BK21), Institute of Agriculture and Life Science, Gyeongsang National University, Jinju 52828, Republic of Korea
| | - Hyun-Jin Kim
- Division of Applied Life Science (BK21), Institute of Agriculture and Life Science, Gyeongsang National University, Jinju 52828, Republic of Korea
| | - Mi Jeong Sung
- Korea Food Research Institute, Wanju-gun 55365, Republic of Korea
| | - Ho Jin Heo
- Division of Applied Life Science (BK21), Institute of Agriculture and Life Science, Gyeongsang National University, Jinju 52828, Republic of Korea
| |
Collapse
|
|
3
|
Kim HJ, Kim N, Jang JY, Kim S, Lee J, Oh HJ. Influence of Cytokine Genetic Polymorphisms in Helicobacter pylori-Associated Gastric Inflammation According to Sex in South Korea. Gut Liver 2024; 18:1002-1013. [PMID: 38388182 PMCID: PMC11565013 DOI: 10.5009/gnl230359] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Revised: 12/20/2023] [Accepted: 12/25/2023] [Indexed: 02/24/2024] Open
Abstract
Background/Aims : The relationship between genetic polymorphisms and gastric inflammation remains unclear. This study aimed to evaluate the impact of genetic polymorphisms on Helicobacter pylori (HP)-associated gastritis according to sex. Methods : Two hundred thirty-two male and 404 female subjects with current HP infection were prospectively enrolled. The genotyping of IL-1B-511 C/T, IL-1RN variable number of tandem repeats, IL-6-572 G/C, IL-8-251 A/T, IL-8-781 C/T, IL-10-1082 G/A, IL-10-592 C/A, TNF-A-308 G/A, and transforming growth factor (TGF)-B-509 C/T, was determined by polymerase chain reaction-restriction fragment length polymorphism. The degree of monocyte or neutrophil infiltration, atrophic gastritis, and intestinal metaplasia was evaluated using the updated Sydney system. Results : Among the male subjects, moderate/severe atrophic gastritis of the corpus was higher in IL-1B-511 CC carriers than in CT and TT carriers independent of age, alcohol consumption, and HP virulence factors (26.9% vs 10.4%; adjusted hazard ratio [HR], 4.377; 95% confidence interval, 1.387 to 13.814). In females, IL-8-251 AA carriers were independently and significantly associated with moderate/severe atrophic gastritis of the corpus compared with that in AT and TT carriers (21.4% vs 6.0%, adjusted HR=3.799). In males, the IL-8-251 TT genotype was associated with moderate/severe intestinal metaplasia of the corpus compared with the AT and AA genotypes (13.4% vs 5.6%, adjusted HR=3.128), while the IL-10-592 CA and CC genotypes were associated with moderate/severe monocyte infiltration of the antrum compared with AA genotype (83.6% vs 71.8%, adjusted HR=2.227). Conclusions : Genetic polymorphisms in cytokines play different roles in HP-associated gastritis according to sex.
Collapse
Affiliation(s)
- Hee Jin Kim
- Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Gyeongsang National University College of Medicine, Changwon, Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
- Department of Medical Device Development, Seoul National University College of Medicine, Seoul, Korea
| | - Jae Young Jang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
- Department of Medical Device Development, Seoul National University College of Medicine, Seoul, Korea
| | - Sihyun Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Jongchan Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Hyeon Jeong Oh
- Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea
| |
Collapse
|
|
4
|
Mao Q, Liu Y, Chen X, Liu CJ. The pertinence of gastric cancer and interleukin 10-819 single nucleotide polymorphisms: a meta-analysis and systematic review. BMC Gastroenterol 2024; 24:76. [PMID: 38365575 PMCID: PMC10874039 DOI: 10.1186/s12876-024-03151-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2023] [Accepted: 01/29/2024] [Indexed: 02/18/2024] Open
Abstract
PURPOSE Cytokines regulate the interaction between the immune system and malignant tumors. Among them, interleukin-10 (IL-10) is a multifunctional anti-inflammatory cytokine mainly produced by immune cells. The correlation between gastric cancer and T/C single nucleotide polymorphism (SNP) of interleukin-10 (IL-10) promoter-819(rs1800871)was opaque and remained to be determined. We aim to explore the pertinence of gastric cancer and SNP of interleukin 10-819 by meta-analysis via five statistical models. METHODS Databases including PubMed, Cochrane Library, Embase, the Scopus, and Google Scholars were comprehensively retrieved for the eligible studies on the related topic from inception to March 2022. Odds ratios (ORs) were generated for dichotomous variants by meta-analysis in each model via STATA 17.0 MP. The statistical models comprised recessive model, over-dominant model, allele model, co-dominant model and dominant model. Subgroup analysis was performed to investigate the difference across races as well as the source of heterogeneity if necessary. RESULTS Eventually a total of 15 articles reporting 7779 patients were enrolled in our study. There were 2383 patients and 5396 controls, collectively. There was no correlation between gastric cancer and IL-10 819 in recessive model, co-dominant model or dominant model, and subgroup analysis showed that Asian, Latin American and Caucasian had no correlation with the risk of gastric cancer. In the allelic model, there was significant correlation between gastric cancer and IL-10 819 (OR = 3.96%, 95%CI: 3.28 to 3.78). In the over-dominant model, there is no correlation between gastric cancer and IL-10 819, but subgroup analysis uncovered significant vulnerability of Asian people with regard to gastric cancer. CONCLUSIONS In our study, both Asians, Latin Americans, and Europeans showed an increased risk of gastric cancer in the allelic model, whereas only Asians showed significant susceptibility in the super dominant model. Of course, more large cohort studies are needed to confirm our results.
Collapse
Affiliation(s)
- Qianqian Mao
- Medical School of Southeast University, 210000, Nanjing, China
| | - Yanwen Liu
- Department of Oncology, Zhongda Hospital, Medical School of Southeast University, 210000, Nanjing, China.
| | - Xi Chen
- School of health, Brooks College (Sunnyvale) the United States of America, Department of epidemiology and statistics, School of public health, Medical College, Zhejiang University, 310000, Hangzhou, China
| | - Cheng Jiang Liu
- Department of General Medicine, Affiliated Anqing First People's Hospital of Anhui Medical University, 246000, Anqing, China
| |
Collapse
|
|
5
|
Malespín-Bendaña W, Alpízar-Alpízar W, Figueroa-Protti L, Reyes L, Molina-Castro S, Une C, Ramírez-Mayorga V. Helicobacter pylori infection induces gastric precancerous lesions and persistent expression of Angpt2, Vegf-A and Tnf-A in a mouse model. Front Oncol 2023; 13:1072802. [PMID: 36874142 PMCID: PMC9975564 DOI: 10.3389/fonc.2023.1072802] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Accepted: 01/26/2023] [Indexed: 02/17/2023] Open
Abstract
Introduction Helicobacter pylori colonizes the gastric mucosa and induces chronic inflammation. Methods Using a mouse model of H. pylori-induced gastritis, we evaluated the mRNA and protein expression levels of proinflammatory and proangiogenic factors, as well as the histopathological changes in gastric mucosa in response to infection. Five- to six-week-old female C57BL/6N mice were challenged with H. pylori SS1 strain. Animals were euthanized after 5-, 10-, 20-, 30-, 40- and 50-weeks post infection. mRNA and protein expression of Angpt1, Angpt2, VegfA, Tnf-α, bacterial colonization, inflammatory response and gastric lesions were evaluated. Results A robust bacterial colonization was observed in 30 to 50 weeks-infected mice, which was accompanied by immune cell infiltration in the gastric mucosa. Compared to non-infected animals, H. pylori-colonized animals showed an upregulation in the expression of Tnf-A, Angpt2 and VegfA at the mRNA and protein levels. In contrast, Angpt1 mRNA and protein expression was downregulated in H. pylori-colonized mice. Conclusion Our data show that H. pylori infection induces the expression of Angpt2, Tnf-A and Vegf-A in murine gastric epithelium. This may contribute to the pathogenesis of H. pylori-associated gastritis, however the significance of this should be further addressed.
Collapse
Affiliation(s)
| | - Warner Alpízar-Alpízar
- Centre for Research on Microscopic Structures (CIEMic), University of Costa Rica, San José, Costa Rica.,Department of Biochemistry, School of Medicine, University of Costa Rica, San José, Costa Rica
| | - Lucía Figueroa-Protti
- Centre for Research on Microscopic Structures (CIEMic), University of Costa Rica, San José, Costa Rica.,Faculty of Microbiology, University of Costa Rica, San José, Costa Rica
| | - Ledis Reyes
- Laboratory for Biological Assays (LEBi), University of Costa Rica, San José, Costa Rica
| | - Silvia Molina-Castro
- Institute of Health Research (INISA), University of Costa Rica, San José, Costa Rica.,Department of Biochemistry, School of Medicine, University of Costa Rica, San José, Costa Rica
| | - Clas Une
- Institute of Health Research (INISA), University of Costa Rica, San José, Costa Rica
| | - Vanessa Ramírez-Mayorga
- Institute of Health Research (INISA), University of Costa Rica, San José, Costa Rica.,Department Public Nutrition, School of Nutrition, University of Costa Rica, San José, Costa Rica
| |
Collapse
|
|
6
|
Maulani C, Auerkari EI, Masulili SLC, Kusdhany LS, Soeroso Y, Soedarsono N. Interferon-Gamma (IFNg) +874A/T Polymorphism Does Not Significantly Affect the Severity of Periodontitis. Eur J Dent 2021; 16:327-332. [PMID: 34784626 PMCID: PMC9339941 DOI: 10.1055/s-0041-1735434] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022] Open
Abstract
OBJECTIVES Interferon-gamma (IFNg) is an immune-regulatory cytokine with a role in host responses to periodontitis. Genetic factors have been reported to modify the corresponding protein expression. The objective of this study was to evaluate the association and role of IFNg polymorphisms, such as IFNg +874 A/T, and the susceptibility to periodontitis. MATERIALS AND METHODS A total of 100 unrelated subjects were included in the present study. Genomic deoxyribonucleic acid (DNA) was obtained from peripheral blood of 43 patients with mild periodontitis and 57 patients with severe periodontitis. The determined clinical parameters of periodontitis included probing depth, clinical attachment loss, and papilla bleeding index. The oral hygiene indicators were also assessed. The level of IFNg was determined from the gingival crevicular fluid by enzyme-linked immunosorbent assay technique. The IFNg +874 A/T polymorphisms were analyzed from peripheral blood by the method of restriction fragment length polymorphism-polymerase chain reaction. STATISTICAL ANALYSIS Statistical analysis of the results was conducted using chi-squared testing for categorical data. Independent t-tests and Mann-Whitney U tests were used for numeric data. Kruskal-Wallis testing was used to compare genotypes concerning for IFNg +874 A/T polymorphism. A p-value < 0.05 was assumed for statistical significance. RESULTS Analysis of the IFNg +874 A/T polymorphism showed no significant differences with the level of IFNg. No significant differences were observed either in IFNg +874 A/T polymorphism between the subjects with mild periodontitis and those with severe periodontitis (p > 0.05). The subjects with severe periodontitis showed marginally but not significantly higher levels of IFNg compared with subjects with mild periodontitis (p > 0.05). CONCLUSION The polymorphism of IFNg +874 A/T was not associated with the level of IFNg nor with the risk of periodontitis in this study.
Collapse
Affiliation(s)
| | - Elza Ibrahim Auerkari
- Department of Oral Biology, Faculty of Dentistry, Universitas Indonesia, Jakarta, Indonesia
| | - Sri Lelyati C Masulili
- Department of Periodontology, Faculty of Dentistry, Universitas Indonesia, Jakarta, Indonesia
| | - Lindawati S Kusdhany
- Department of Prosthodontics, Faculty of Dentistry, Universitas Indonesia, Jakarta, Indonesia
| | - Yuniarti Soeroso
- Department of Periodontology, Faculty of Dentistry, Universitas Indonesia, Jakarta, Indonesia
| | - Nurtami Soedarsono
- Department of Oral Biology, Faculty of Dentistry, Universitas Indonesia, Jakarta, Indonesia
| |
Collapse
|
|
7
|
Kaminsky LW, Al-Sadi R, Ma TY. IL-1β and the Intestinal Epithelial Tight Junction Barrier. Front Immunol 2021; 12:767456. [PMID: 34759934 PMCID: PMC8574155 DOI: 10.3389/fimmu.2021.767456] [Citation(s) in RCA: 225] [Impact Index Per Article: 56.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Accepted: 10/11/2021] [Indexed: 02/06/2023] Open
Abstract
The intestinal epithelial tight junction (TJ) barrier controls the paracellular permeation of contents from the intestinal lumen into the intestinal tissue and systemic circulation. A defective intestinal TJ barrier has been implicated as an important pathogenic factor in inflammatory diseases of the gut including Crohn's disease, ulcerative colitis, necrotizing enterocolitis, and celiac disease. Previous studies have shown that pro-inflammatory cytokines, which are produced during intestinal inflammation, including interleukin-1β (IL-1β), tumor necrosis factor-α, and interferon-γ, have important intestinal TJ barrier-modulating actions. Recent studies have shown that the IL-1β-induced increase in intestinal TJ permeability is an important contributing factor of intestinal inflammation. The IL-1β-induced increase in intestinal TJ permeability is mediated by regulatory signaling pathways and activation of nuclear transcription factor nuclear factor-κB, myosin light chain kinase gene activation, and post-transcriptional occludin gene modulation by microRNA and contributes to the intestinal inflammatory process. In this review, the regulatory role of IL-1β on intestinal TJ barrier, the intracellular mechanisms that mediate the IL-1β modulation of intestinal TJ permeability, and the potential therapeutic targeting of the TJ barrier are discussed.
Collapse
Affiliation(s)
- Lauren W Kaminsky
- Section of Allergy, Asthma, and Immunology, Department of Medicine, Pennsylvania State University College of Medicine, Hershey, PA, United States
| | - Rana Al-Sadi
- Division of Gastroenterology and Hepatology, Department of Medicine, Pennsylvania State University College of Medicine, Hershey, PA, United States
| | - Thomas Y Ma
- Division of Gastroenterology and Hepatology, Department of Medicine, Pennsylvania State University College of Medicine, Hershey, PA, United States
| |
Collapse
|
|
8
|
Association of Interleukin-10 Polymorphisms with Susceptibility to Colorectal Cancer and Gastric Cancer: an Updated Meta-analysis Based on 106 Studies. J Gastrointest Cancer 2021; 53:1066-1082. [PMID: 34694592 DOI: 10.1007/s12029-021-00685-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/01/2021] [Indexed: 01/30/2023]
Abstract
BACKGROUND The purpose of this study was to explore the association of IL-10 polymorphisms with susceptibility to colorectal cancer (CRC) and gastric cancer (GC). METHODS PubMed, Scopus, Embase, SciELO, medRxiv, China Biology Medicine Disc, DeepDyve, CNKI, and Web of Science were used to identify all relevant articles published up to 20th June 2021, without any restrictions on ethnicity. Summary odds ratios (ORs) with 95% confidence intervals (CIs) were used to determine the strength of the associations. RESULTS A total of 106 case-control studies were included. For CRC, 15 studies with 2772 cases and 3719 controls on -1082A/G, 11 studies with 3259 cases and 4992 controls on -592C/A, and 3 studies with 477 cases and 544 controls on -819 T/C were selected. For GC, 31 studies with 6229 cases and 8666 controls on -1082A/G, 27 studies with 5457 cases and 8381 controls on -592C/A, and 19 studies with 3556 cases and 6218 controls on -819 T/C were included. Pooled data showed a significant association between IL-10-819 T/C polymorphism and CRC susceptibility in overall population, but not for IL-10-1082A/G and -592C/A polymorphisms. However, IL-10-592C/A polymorphism was associated with CRC risk in Asians. A significant association of IL-10-1082A/G polymorphism with the GC risk was found. In the ethnicity subgroup analysis, a significant association was found between IL-10-1082A/G polymorphism and GC risk among Asians. The IL-10-819 T/C was not associated with GC risk in overall population and by ethnicity. CONCLUSIONS Our pooled data show a significant association of IL-10-819 T/C and IL-10-1082A/G polymorphisms with CRC and GC in overall population, respectively. However, other factors may influence these associations, and large-scale studies with adequate methodological quality are necessary to confirm the impact on CRC and GC risk.
Collapse
|
|
9
|
Al-Amodi HS, Abdelsattar S, Kasemy ZA, Bedair HM, Elbarbary HS, Kamel HFM. Potential Value of TNF-α (-376 G/A) Polymorphism and Cystatin C (CysC) in the Diagnosis of Sepsis Associated Acute Kidney Injury (S-AK I) and Prediction of Mortality in Critically Ill patients. Front Mol Biosci 2021; 8:751299. [PMID: 34692772 PMCID: PMC8526786 DOI: 10.3389/fmolb.2021.751299] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Accepted: 09/20/2021] [Indexed: 12/29/2022] Open
Abstract
Sepsis Associated Kidney Injury represents a major health concern as it is frequently associated with increased risk of mortality and morbidity. We aimed to evaluate the potential value of TNF-α (-376 G/A) and cystatin C in the diagnosis of S-AKI and prediction of mortality in critically ill patients. This study included 200 critically ill patients and 200 healthy controls. Patients were categorized into 116 with acute septic shock and 84 with sepsis, from which 142 (71%) developed S-AKI. Genotyping of TNF-α (-376 G/A) was performed by RT-PCR and serum CysC was assessed by Enzyme Linked Immunosorbent Assay. Our results showed a highly significant difference in the genotype frequencies of TNF-α (-376 G/A) SNP between S-AKI and non-AKI patients (p < 0.001). Additionally, sCysC levels were significantly higher in the S-AKI group (p = 0.011). The combination of both sCysC and TNF-α (-376 G/A) together had a better diagnostic ability for S-AKI than sCysC alone (AUC = 0.610, 0.838, respectively). Both GA and AA genotypes were independent predictors of S-AKI (p= < 0.001, p = 0.002 respectively). Additionally, sCysC was significantly associated with the risk of S-AKI development (Odds Ratio = 1.111). Both genotypes and sCysC were significant predictors of non-survival (p < 0.001), suggesting their potential role in the diagnosis of S-AKI and prediction of mortality.
Collapse
Affiliation(s)
- Hiba S Al-Amodi
- Biochemistry Department, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Shimaa Abdelsattar
- Clinical Biochemistry and Molecular Diagnostics Department, National Liver Institute, Menoufia University, Shebine Elkoum, Egypt
| | - Zeinab A. Kasemy
- Department of Public Health and Community Medicine, Faculty of Medicine, Menoufia University, Shebine Elkoum, Egypt
| | - Hanan M. Bedair
- Clinical Pathology Department, National Liver Institute, Menoufia University, Shebine Elkoum, Egypt
| | - Hany S. Elbarbary
- Department of Internal Medicine, Renal Unit, Faculty of Medicine, Menoufia University, Shebine Elkoum, Egypt
- Department of Internal Medicine, Renal Unit, Faculty of Medicine, King Faisal University, Al-Ahsa, Saudi Arabia
| | - Hala F. M. Kamel
- Biochemistry Department, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia
- Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| |
Collapse
|
|
10
|
Miller AK, Tavera G, Dominguez RL, Camargo MC, Waterboer T, Wilson KT, Williams SM, Morgan DR. Ornithine decarboxylase (ODC1) gene variant (rs2302615) is associated with gastric cancer independently of Helicobacter pylori CagA serostatus. Oncogene 2021; 40:5963-5969. [PMID: 34376808 PMCID: PMC8692072 DOI: 10.1038/s41388-021-01981-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 07/08/2021] [Accepted: 07/22/2021] [Indexed: 02/07/2023]
Abstract
The primary cause of gastric cancer is chronic infection with Helicobacter pylori (H. pylori), particularly the high-risk genotype cagA, and risk modification by human genetic variants. We studied 94 variants in 54 genes for association with gastric cancer, including rs2302615 in ornithine decarboxylase (ODC1), which may affect response to chemoprevention with the ODC inhibitor, eflornithine (difluoromethylornithine; DFMO). Our population-based, case-control study included 1366 individuals (664 gastric cancer cases and 702 controls) from Western Honduras, a high incidence region of Latin America. CagA seropositivity was strongly associated with cancer (OR = 3.6; 95% CI: 2.6, 5.1). The ODC1 variant rs2302615 was associated with gastric cancer (OR = 1.36; p = 0.018) in a model adjusted for age, sex, and CagA serostatus. Two additional single nucleotide polymorphisms (SNPs) in CASP1 (rs530537) and TLR4 (rs1927914) genes were also associated with gastric cancer in univariate models as well as models adjusted for age, sex, and CagA serostatus. The ODC1 SNP association with gastric cancer was stronger in individuals who carried the TT genotype at the associating TLR4 polymorphism, rs1927914 (OR = 1.77; p = 1.85 × 10-3). In conclusion, the ODC1 variant, rs2302615, is associated with gastric cancer and supports chemoprevention trials with DFMO, particularly in individuals homozygous for the T allele at rs1927914.
Collapse
Affiliation(s)
- Anna K Miller
- Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH, USA
| | - Gloria Tavera
- Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA
| | - Ricardo L Dominguez
- Hospital de Occidente, Ministry of Health, Santa Rosa de Copan, Copan, Honduras
| | - M Constanza Camargo
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
| | - Tim Waterboer
- Infections and Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Keith T Wilson
- Vanderbilt University Medical Center, Division of Gastroenterology, Hepatology, and Nutrition, Nashville, TN, USA
- Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN, USA
| | - Scott M Williams
- Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH, USA.
- Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA.
| | - Douglas R Morgan
- UAB Division of Gastroenterology and Hepatology, The University of Alabama at Birmingham (UAB), Birmingham, AL, USA.
| |
Collapse
|
|
11
|
Lee Y, Lee SM, Choi J, Kang S, So S, Kim D, Ahn JY, Jung HY, Jeong JY, Kang E. Mitochondrial DNA Haplogroup Related to the Prevalence of Helicobacter pylori. Cells 2021; 10:cells10092482. [PMID: 34572132 PMCID: PMC8469812 DOI: 10.3390/cells10092482] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Revised: 09/13/2021] [Accepted: 09/16/2021] [Indexed: 11/16/2022] Open
Abstract
Mitochondria are essential organelles that are not only responsible for energy production but are also involved in cell metabolism, calcium homeostasis, and apoptosis. Targeting mitochondria is a key strategy for bacteria to subvert host cells' physiology and promote infection. Helicobacter (H.) pylori targets mitochondria directly. However, mitochondrial genome (mtDNA) polymorphism (haplogroup) is not yet considered an important factor for H. pylori infection. Here, we clarified the association of mitochondrial haplogroups with H. pylori prevalence and the ability to perform damage. Seven mtDNA haplogroups were identified among 28 H. pylori-positive subjects. Haplogroup B was present at a higher frequency and haplotype D at a lower one in the H. pylori population than in that of the H. pylori-negative one. The fibroblasts carrying high-frequency haplogroup displayed a higher apoptotic rate and diminished mitochondrial respiration following H. pylori infection. mtDNA mutations were accumulated more in the H. pylori-positive population than in that of the H. pylori-negative one in old age. Among the mutations, 57% were located in RNA genes or nonsynonymous protein-coding regions in the H. pylori-positive population, while 35% were in the H. pylori-negative one. We concluded that gastric disease caused by Helicobacter virulence could be associated with haplogroups and mtDNA mutations.
Collapse
Affiliation(s)
- Yeonmi Lee
- Department of Biomedical Science, College of Life Science and Center for Embryo and Stem Cell Research, CHA Advanced Research Institute, CHA University, Seongnam, Gyeonggi 13488, Korea; (Y.L.); (J.C.); (S.K.); (S.S.)
| | - Sun-Mi Lee
- Asan Medical Center, Asan Institute for Life Sciences, Seoul 05505, Korea;
| | - Jiwan Choi
- Department of Biomedical Science, College of Life Science and Center for Embryo and Stem Cell Research, CHA Advanced Research Institute, CHA University, Seongnam, Gyeonggi 13488, Korea; (Y.L.); (J.C.); (S.K.); (S.S.)
| | - Seoon Kang
- Department of Biomedical Science, College of Life Science and Center for Embryo and Stem Cell Research, CHA Advanced Research Institute, CHA University, Seongnam, Gyeonggi 13488, Korea; (Y.L.); (J.C.); (S.K.); (S.S.)
| | - Seongjun So
- Department of Biomedical Science, College of Life Science and Center for Embryo and Stem Cell Research, CHA Advanced Research Institute, CHA University, Seongnam, Gyeonggi 13488, Korea; (Y.L.); (J.C.); (S.K.); (S.S.)
- Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea
| | - Deokhoon Kim
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea;
| | - Ji-Yong Ahn
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea;
| | - Hwoon-Yong Jung
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea;
- Correspondence: (H.-Y.J.); (J.-Y.J.); (E.K.); Tel.: +82-2-3010-3197 (H.-Y.J.); +82-2-3010-4105 (J.-Y.J.); +82-31-881-7846 (E.K.)
| | - Jin-Yong Jeong
- Asan Medical Center, Asan Institute for Life Sciences, Seoul 05505, Korea;
- Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea
- Correspondence: (H.-Y.J.); (J.-Y.J.); (E.K.); Tel.: +82-2-3010-3197 (H.-Y.J.); +82-2-3010-4105 (J.-Y.J.); +82-31-881-7846 (E.K.)
| | - Eunju Kang
- Department of Biomedical Science, College of Life Science and Center for Embryo and Stem Cell Research, CHA Advanced Research Institute, CHA University, Seongnam, Gyeonggi 13488, Korea; (Y.L.); (J.C.); (S.K.); (S.S.)
- Correspondence: (H.-Y.J.); (J.-Y.J.); (E.K.); Tel.: +82-2-3010-3197 (H.-Y.J.); +82-2-3010-4105 (J.-Y.J.); +82-31-881-7846 (E.K.)
| |
Collapse
|
|
12
|
The Role of Tumor Necrosis Factor-α (TNF-α) Polymorphisms in Gastric Cancer: a Meta-Analysis. J Gastrointest Cancer 2021; 53:756-769. [PMID: 34478034 DOI: 10.1007/s12029-021-00688-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/08/2021] [Indexed: 12/12/2022]
Abstract
PURPOSE Tumor necrosis factor alpha (TNF-α) is an inflammatory cytokine which may play a role in the development of gastric cancer (GC). This study aimed to investigate the association of five TNF-α polymorphisms including TNF-α-857, TNF-α-1031, TNF-α-863, TNF-α-308, and TNF-α-238 polymorphisms with GC risk. METHODS All eligible case-control studies were collected by searching PubMed, Scopus, and Web of Science. The association of the risk of GC with TNF-α polymorphisms was estimated using odds ratio (OR) and 95% confidence interval (CI). Heterogeneity was assessed via Cochrane's Q and I2 analyses. RESULTS A total of 46 publications involving 16, 715 cases with GC and 27, 998 controls were recruited. The study revealed a significant association for TNF-α 308 (recessive model: OR = 0.646, P = 0.035), TNF-α-1031 (homozygote model: OR = 1.584, P = 0.027), and TNF-α-857 (homozygote model: OR = 1.760, P = 0.001) polymorphisms with the GC risk. The results of subgroup analysis based ethnicity found a significant association between GC risk and TNF-α-857 polymorphism in Caucasian subgroup (P = 0.005) and TNF-α-1031 polymorphism and GC risk in Asians (P = 0.018). CONCLUSIONS This study suggested that TNF-α-857 and TNF-α-1031 polymorphisms may be associated with the increased gastric cancer risk.
Collapse
|
|
13
|
Ben Selma W, Laribi AB, Alibi S, Boukadida J. Association of an IFN-γ variant with susceptibility to chronic hepatitis B by the enhancement of HBV DNA replication. Cytokine 2021; 143:155525. [PMID: 33896709 DOI: 10.1016/j.cyto.2021.155525] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Revised: 03/21/2021] [Accepted: 03/29/2021] [Indexed: 02/07/2023]
Abstract
Interferon gamma (IFN-γ) is a crucial cytokine in host immune response to hepatitis B virus (HBV) infection. This study aimed to determine whether a functional polymorphism +874T/A in IFN-γ gene linked to high and low producer phenotypes [IFN-γ (+874Thigh → Alow)] may alter the outcomes of chronic HBV infection in Tunisian population. The +874T/A was analysed by ARMS-PCR method in the group of 200 patients chronically infected with HBV and 200 healthy controls. We observed that minor +874A allele, minor +874AA and +874TA genotypes were significantly more frequent in the chronic hepatitis B group in comparison to the control group [49 vs. 31%, P < 10-4; 24 vs. 13%, P < 10-4; 52 vs. 38%, P < 10-4; respectively]. Besides, they were associated with susceptibility to hepatitis B infection [OR = 2.15, 3.87 and 2.84, respectively]. The minor +874A allele and +874AA genotype were statistically more representative in the sub-group of patients with high viral DNA load when compared with the sub-group of patients with low HBV DNA load [(57% vs. 43%, P = 0.003, OR = 1.79); (33% vs. 14%, P = 0.003, OR = 3.59), respectively]. Collectively, our study suggests an association between the IFN-γ +874T/A SNP and persistence of HBV by the enhancement of HBV DNA replication.
Collapse
Affiliation(s)
- Walid Ben Selma
- Laboratory of Microbiology, UR12SP34, University Hospital Farhat Hached, Sousse, Tunisia; Laboratory of Biological and Genetic Markers Studying for Early Diagnosis and Follow-up of Neurological Diseases, LR18ES47, Faculty of Medicine, Sousse, Tunisia; Higher Institute of Applied Sciences and Technology, Mahdia, Tunisia.
| | - Ahmed Baligh Laribi
- Laboratory of Microbiology, UR12SP34, University Hospital Farhat Hached, Sousse, Tunisia
| | - Sana Alibi
- Laboratory of Microbiology, UR12SP34, University Hospital Farhat Hached, Sousse, Tunisia
| | - Jalel Boukadida
- Laboratory of Microbiology, UR12SP34, University Hospital Farhat Hached, Sousse, Tunisia; Laboratory of Biological and Genetic Markers Studying for Early Diagnosis and Follow-up of Neurological Diseases, LR18ES47, Faculty of Medicine, Sousse, Tunisia
| |
Collapse
|
|
14
|
Malespín-Bendaña W, Machado JC, Une C, Alpízar-Alpízar W, Molina-Castro S, Ramírez-Mayorga V. The TNF-A-857*T Polymorphism is Associated with Gastric Adenocarcinoma Risk in a Costa Rican Population. Am J Med Sci 2021; 362:182-187. [PMID: 34088492 DOI: 10.1016/j.amjms.2021.01.017] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2020] [Revised: 10/20/2020] [Accepted: 01/28/2021] [Indexed: 01/22/2023]
Abstract
BACKGROUND Costa Rica is ranked as one of the countries with highest incidence of gastric cancer worldwide. Previous studies in Costa Rican populations have revealed associations between gastric cancer risk and several cytokine polymorphisms that seem to play a role in the regulation of the expression of these proteins. In this study, we assessed associations of the polymorphisms IL-6-174 G/C, IFNGR1-56 C/T, IL-8-251 T/A and TNF-A (-857 C/T, -308 A/G) with gastric pathologies in a high-risk population of Latin America. METHODS DNA samples of 47 patients with gastric adenocarcinoma, 53 with chronic gastritis, 56 with duodenal ulcer and 94 healthy controls, were genotyped for the five mentioned SNPs. All participants were ≥50-years-old. Genotyping was performed by PCR-RFLP and 5'-nuclease PCR assay. H. pylori infection, CagA status, pepsinogen (PG) I and II blood levels were determined by ELISA. Logistic regression analysis was used to determine possible associations of the polymorphisms with cancer, gastritis and duodenal ulcer, and linear regression analysis to determine associations with blood PG levels. RESULTS A total of 86.6% of the population was positive for H. pylori; of them, 51.6% was CagA+. Patients with the TNF-A-857*T allele had an increased risk for gastritis (OR: 3.67, p = 0.015) and gastric adenocarcinoma (OR:6.15, p = 0.001). Associations between other polymorphisms and gastric diseases, or PG levels, were not found. CONCLUSIONS Our results indicate that the TNF-A-857*T SNP is among the risk factors associated with the risk of gastric cancer in Costa Rica.
Collapse
Affiliation(s)
- Wendy Malespín-Bendaña
- Institute of Health Research (INISA), University of Costa Rica, Costa Rica; School of Medicine, University of Costa Rica, Costa Rica.
| | - José Carlos Machado
- Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Portugal.
| | - Clas Une
- Institute of Health Research (INISA), University of Costa Rica, Costa Rica.
| | - Warner Alpízar-Alpízar
- Centre for Research on Microscopic Structures (CIEMic), University of Costa Rica, Costa Rica; Department of Biochemistry, School of Medicine, University of Costa Rica, Costa Rica.
| | - Silvia Molina-Castro
- Institute of Health Research (INISA), University of Costa Rica, Costa Rica; Department of Biochemistry, School of Medicine, University of Costa Rica, Costa Rica.
| | - Vanessa Ramírez-Mayorga
- Institute of Health Research (INISA), University of Costa Rica, Costa Rica; Department of Public Nutrition, School of Nutrition, University of Costa Rica, Costa Rica.
| |
Collapse
|
|
15
|
Kirik FE, Ülger M, Tezcan Ülger S, Aslan G. Association of cytokine gene polymorphisms with susceptibility to cutaneous leishmaniasis in a Turkish population. Parasite Immunol 2020; 42:e12775. [PMID: 32656817 DOI: 10.1111/pim.12775] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2020] [Accepted: 07/08/2020] [Indexed: 01/29/2023]
Abstract
AIMS The objective of this study was to determine the association of TNF-α -308 G/A, IFN-γ +874 T/A, IL-12B + 1188 A/C, IL-10 -1082 G/A and IL-4 -590 C/T polymorphisms with susceptibility to CL. METHODS AND RESULTS A total of 55 CL patients and 110 controls from Sanlıurfa province of Turkey were included to this study. Polymorphisms were genotyped by 'polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)' and 'amplification refractory mutation system-PCR (ARMS-PCR)' methods. A statistically significant difference was noted in the allele (P < .001, P = .002) and genotype (P < .001, P = .001,) frequencies of TNF-α -308 G/A and IL-4 -590 C/T, respectively. TNF-α 308 GG versus GA genotype (OR = 19.556 [95% CI 8.310-46.019] P < .001), GG versus GA + AA genotype (OR = 20.444 [95% CI 8.707-48.004] P < .001) and G versus A allele (OR = 6.968 [95% CI 3.903-12.440] P < .001) revealed significant association with CL. IL-4 -590 CC versus TT + CT genotype (OR = 2.049 [95% CI 1.025-4.096], P = .041) and C versus T allele (OR = 2.441 [95% CI 1.355-4.396], P = .002) revealed significant association with CL. CONCLUSION Our study indicates that TNF-α 308 G/A and IL-4-590 C/T polymorphisms are significantly associated with susceptibility to CL. Individuals carrying A allele at TNF-α promoter -308 position and T allele at IL-4 promoter -590 position are at a higher risk for CL.
Collapse
Affiliation(s)
- Fatma Esin Kirik
- Department of Medical Microbiology, Faculty of Medicine, Nigde Ömer Halisdemir University, Niğde, Turkey
| | - Mahmut Ülger
- Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Mersin University, Mersin, Turkey
| | - Seda Tezcan Ülger
- Department of Medical Microbiology, Faculty of Medicine, Mersin University, Mersin, Turkey
| | - Gönül Aslan
- Department of Medical Microbiology, Faculty of Medicine, Mersin University, Mersin, Turkey
| |
Collapse
|
|
16
|
Seeger AY, Ringling MD, Zohair H, Blanke SR. Risk factors associated with gastric malignancy during chronic Helicobacter pylori Infection. MEDICAL RESEARCH ARCHIVES 2020; 8:2068. [PMID: 37655156 PMCID: PMC10470974 DOI: 10.18103/mra.v8i3.2068] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/02/2023]
Abstract
Chronic Helicobacter pylori (Hp) infection is considered to be the single most important risk factor for the development of gastric adenocarcinoma in humans, which is a leading cause of cancer-related death worldwide. Nonetheless, Hp infection does not always progress to malignancy, and, gastric adenocarcinoma can occur in the absence of detectable Hp carriage, highlighting the complex and multifactorial nature of gastric cancer. Here we review known contributors to gastric malignancy, including Hp virulence factors, host genetic variation, and multiple environmental variables. In addition, we assess emerging evidence that resident gastric microflora in humans might impact disease progression in Hp-infected individuals. Molecular approaches for microbe identification have revealed differences in the gastric microbiota composition between cancer and non-cancerous patients, as well as infected and uninfected individuals. Although the reasons underlying differences in microbial community structures are not entirely understood, gastric atrophy and hypochlorhydria that accompany chronic Hp infection may be a critical driver of gastric dysbiosis that promote colonization of microbes that contribute to increased risk of malignancy. Defining the importance and role of the gastric microbiota as a potential risk factor for Hp-associated gastric cancer is a vital and exciting area of current research.
Collapse
Affiliation(s)
- Ami Y. Seeger
- Department of Microbiology, School of Molecular and Cellular Biology, College of Liberal Arts and Sciences, University of Illinois Urbana-Champaign, Urbana, Illinois, 61801
| | - Megan D. Ringling
- Department of Microbiology, School of Molecular and Cellular Biology, College of Liberal Arts and Sciences, University of Illinois Urbana-Champaign, Urbana, Illinois, 61801
| | - Huzaifa Zohair
- Department of Microbiology, School of Molecular and Cellular Biology, College of Liberal Arts and Sciences, University of Illinois Urbana-Champaign, Urbana, Illinois, 61801
| | - Steven R. Blanke
- Department of Microbiology, School of Molecular and Cellular Biology, College of Liberal Arts and Sciences, University of Illinois Urbana-Champaign, Urbana, Illinois, 61801
- Department of Pathobiology, College of Veterinary Medicine, University of Illinois Urbana-Champaign, Urbana, Illinois, 61801
- Biomedical and Translational Sciences Department, Carle Illinois College of Medicine, University of Illinois Urbana-Champaign, Urbana, Illinois, 61801
| |
Collapse
|
|
17
|
Jahromi M, Al-Otaibi T, Othman N, Gheith O, Mahmoud T, Nair P, Halim MA, Nampoory N. Immunogenetics of new onset diabetes after transplantation in Kuwait. Diabetes Metab Syndr Obes 2019; 12:731-742. [PMID: 31190933 PMCID: PMC6535099 DOI: 10.2147/dmso.s195859] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2018] [Accepted: 03/07/2019] [Indexed: 01/14/2023] Open
Abstract
Introduction and aim: New onset diabetes after transplantation (NODAT) is a serious metabolic complication following kidney transplantation. Although beta-cell dysfunction is considered the main contributing factor in the development of this complication, its exact etiology is yet to be identified. We aimed to investigate NODAT among kidney transplant cohort in Kuwait with special stress on correlation between its risk factors and interferon gamma genotyping. Materials and methods: We surveyed 309 kidney transplant recipients from Hamed Al Essa Transplantation Centre, Kuwait. The participants were categorized into cohorts according to the development of NODAT diagnosed based on the American Diabetes Association guidelines. Statistical analyses were performed using SPSS software. We genotyped interferon gamma as the leading immunosignature for T lymphocyte. Results: No relationship between ethnicity and the development of NODAT was identified. However, there was a significant difference in age between cohorts. Younger patients demonstrated a lower rate of NODAT while, NODAT reached its maximum in 40-60-year age group. IFNG TT genotype was significantly associated with NODAT (p=0.005), while IFNG AA was considerably higher in the non-NODAT group. Conclusion: Beside the conventional contributing factors of NODAT, our results might represent a suitable platform for a larger cytokine and chemokine spectrum genotyping.
Collapse
Affiliation(s)
- Mohamed Jahromi
- Clinical Research, Medical Division, Dasman Diabetes Institute, Kuwait City, Kuwait
| | - Torki Al-Otaibi
- Nephrology Department, Hamid Al-Essa Organ Transplant Center, Kuwait City, Kuwait
| | - Nashwa Othman
- Education, Clinical Services Division, Dasman Diabetes Institute, Kuwait City, Kuwait
| | - Osama Gheith
- Nephrology Department, Hamid Al-Essa Organ Transplant Center, Kuwait City, Kuwait
| | - Tarek Mahmoud
- Nephrology Department, Hamid Al-Essa Organ Transplant Center, Kuwait City, Kuwait
| | - Prasad Nair
- Nephrology Department, Hamid Al-Essa Organ Transplant Center, Kuwait City, Kuwait
| | - Medhat A Halim
- Nephrology Department, Hamid Al-Essa Organ Transplant Center, Kuwait City, Kuwait
| | - Narayanam Nampoory
- Clinical Research, Medical Division, Dasman Diabetes Institute, Kuwait City, Kuwait
- Nephrology Department, Hamid Al-Essa Organ Transplant Center, Kuwait City, Kuwait
| |
Collapse
|
|
18
|
Zendehdel A, Roham M. Biological evidence of the relationship between
Helicobacter pylori
and associated extragastric diseases. J Cell Biochem 2019; 120:12128-12140. [PMID: 30977160 DOI: 10.1002/jcb.28681] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2018] [Revised: 02/07/2019] [Accepted: 02/14/2019] [Indexed: 12/14/2022]
Affiliation(s)
- Abolfazl Zendehdel
- Department of Geriatric Medicine, Ziaeian Hospital Tehran University of Medical Sciences Tehran Iran
| | - Maryam Roham
- Antimicrobial‐Resistant Research Center Iran University of Medical Sciences Tehran Iran
| |
Collapse
|
|
19
|
Moghmi M, Arjmandi A, Aghili K, Jafari M, Zare-Shehneh M, Rastegar S, Abolbaghaei SM, Neamatzadeh H. ASSOCIATION OF INTERLEUKIN-10 -592A>C AND -819T>C POLYMORPHISMS WITH GASTRIC CANCER RISK: A SYSTEMATIC REVIEW AND META-ANALYSIS OF 44 CASE-CONTROL STUDIES. ABCD-ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA 2019; 32:e1415. [PMID: 30624524 PMCID: PMC6323628 DOI: 10.1590/0102-672020180001e1415] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/21/2018] [Accepted: 10/11/2018] [Indexed: 12/14/2022]
Abstract
INTRODUCTION A series of studies have evaluated the association between -592A>C and -819T>C polymorphisms in the promoter regions of Interleukin-10 (IL-10) and gastric cancer (GC) risk. However, the results remain inconclusive. OBJECTIVE To better understand the association of the polymorphisms with GC risk, we performed a comprehensive meta-analysis. METHOD An electronic search was performed of several databases to identify relevant studies up to April 2018. RESULTS A total of 44 case-control studies, including 26 studies on IL-10 -592A>C (5,332 cases and 8,272 controls) and 18 studies on IL-10 -819T>C (3,431 cases and 6,109 controls) were selected. Overall, -592A>C polymorphism was associated with the risk of GC under the heterozygote model (OR=1.153, 95% CI=1.020-1.305, p=0.023), but not -819T>C polymorphism. When stratified by ethnicity, significant association was only observed in the Asians under the allele model (OR=1.153, 95% CI=1.007-1.320, p=0.040) and the heterozygote model (OR=1.218, 95% CI=1.076-1.379, p=0.002) for -592A>C. CONCLUSION The current meta-analysis results inconsistent with previous meta-analyses; showed that the IL-10 -592A>C polymorphism, but not -819T>C polymorphism, may be contributed to the susceptibility of GC in overall and Asian populations.
Collapse
Affiliation(s)
- Mansour Moghmi
- Shahid Sadoughi University of Medical Sciences, Pathology, Yazd, Yazd
| | - Amir Arjmandi
- Shahid Sadoughi University of Medical Sciences, Medical Genetics, Yazd, Yazd
| | - Kazem Aghili
- Shahid Sadoughi University of Medical Sciences, Radiology, Yazd, Yazd
| | - Mohammadali Jafari
- Shahid Sadoughi University of Medical Sciences, Emergency Medicine, Yazd, Yazd
| | - Masoud Zare-Shehneh
- Shahid Sadoughi University of Medical Sciences, Medical Genetics, Yazd, Yazd
| | - Shohreh Rastegar
- Shahid Sadoughi University of Medical Sciences, Anesthesiology, Yazd, Yazd
| | | | - Hossein Neamatzadeh
- Shahid Sadoughi University of Medical Sciences, Medical Genetics, Yazd, Yazd
| |
Collapse
|
|
20
|
Genetic Polymorphisms in Inflammatory and Other Regulators in Gastric Cancer: Risks and Clinical Consequences. Curr Top Microbiol Immunol 2019; 421:53-76. [PMID: 31123885 DOI: 10.1007/978-3-030-15138-6_3] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Helicobacter pylori infection is associated with the development of a chronic inflammatory response, which may induce peptic ulcers, gastric cancer (GC), and mucosa-associated lymphoid tissue (MALT) lymphoma. Chronic H. pylori infection promotes the genetic instability of gastric epithelial cells and interferes with the DNA repair systems in host cells. Colonization of the stomach with H. pylori is an important cause of non-cardia GC and gastric MALT lymphoma. The reduction of GC development in patients who underwent anti-H. pylori eradication schemes has also been well described. Individual susceptibility to GC development depends on the host's genetic predisposition, H. pylori virulence factors, environmental conditions, and geographical determinants. Biological determinants are urgently sought to predict the clinical course of infection in individuals with confirmed H. pylori infection. Possible candidates for such biomarkers include genetic aberrations such as single-nucleotide polymorphisms (SNPs) found in various cytokines/growth factors (e.g., IL-1β, IL-2, IL-6, IL-8, IL-10, IL-13, IL-17A/B, IFN-γ, TNF, TGF-β) and their receptors (IL-RN, TGFR), innate immunity receptors (TLR2, TLR4, CD14, NOD1, NOD2), enzymes involved in signal transduction cascades (PLCE1, PKLR, PRKAA1) as well as glycoproteins (MUC1, PSCA), and DNA repair enzymes (ERCC2, XRCC1, XRCC3). Bacterial determinants related to GC development include infection with CagA-positive (particularly with a high number of EPIYA-C phosphorylation motifs) and VacA-positive isolates (in particular s1/m1 allele strains). The combined genotyping of bacterial and host determinants suggests that the accumulation of polymorphisms favoring host and bacterial features increases the risk for precancerous and cancerous lesions in patients.
Collapse
|
|
21
|
An updated association between TNF-α -238G/A polymorphism and gastric cancer susceptibility in East Asians. Biosci Rep 2018; 38:BSR20181231. [PMID: 30413607 PMCID: PMC6294626 DOI: 10.1042/bsr20181231] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2018] [Revised: 10/20/2018] [Accepted: 11/06/2018] [Indexed: 12/13/2022] Open
Abstract
Polymorphisms in the tumor necrosis factor α (TNF-α) gene are emerging as key determinants of gastric diseases. The TNF-α-238G/A single-nucleotide polymorphism (SNP) is the most extensively studied. However, this association is inconsistent amongst different populations. We therefore conducted an updated meta-analysis to obtain a more precise estimate of the association of TNF-α-238G/A polymorphism with gastric cancer (GC) risk. A comprehensive search of PubMed, Embase, Chinese (CNKI and WanFang) databases was performed to identify relevant studies through 5 May 2018. Odds ratio (OR) and 95% confidence interval (CI) were used to assess the strength of the association. Fourteen studies were included in our meta-analysis involving 2999 cases and 4685 controls. There was no significant association between TNF-α-238G/A polymorphism and GC risk in the overall populations. In the subgroup analysis, we found that TNF-α-238G/A polymorphism was associated with the increased risk of GC amongst Asians, especially in Chinese, but not in Caucasians. Subgroup analysis by genotyping methods revealed increased risk for other methods. In conclusion, our present meta-analysis shows that TNF-α-238G/A polymorphism is associated with the risk of GC in East Asian individuals.
Collapse
|
|
22
|
Lin W, Li L, Chen J, Li D, Hou J, Guo H, Shen J. Long-term crowding stress causes compromised nonspecific immunity and increases apoptosis of spleen in grass carp (Ctenopharyngodon idella). FISH & SHELLFISH IMMUNOLOGY 2018; 80:540-545. [PMID: 29964198 DOI: 10.1016/j.fsi.2018.06.050] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/24/2018] [Revised: 06/18/2018] [Accepted: 06/27/2018] [Indexed: 05/25/2023]
Abstract
Crowding stress is one of the most common environmental stressors in intensive aquaculture. To investigate the influences of long-term crowding stress on nonspecific immune responses and apoptosis in fish, grass carp (Ctenopharyngodon idella) were cultured at low (0.9 kg m-2), medium (2.97 kg m-2) and high (5.9 kg m-2) stocking densities for 10 weeks in the present study. The results showed that elevation of stocking densities caused splenic tissue damages and inflammatory responses, which are characterized with the formation of melano-macrophage centers and the increase of granulocytes as well as significant upregulation of inflammatory cytokine genes (il1β and tnfα). The remarkable decline in the activities of serum lysozyme, acid phosphatase and alkaline phosphatase under high stocking density further confirmed that increased stocking density affected fish nonspecific immune response negatively. Moreover, the transcriptional levels of splenic apoptotic-related genes caspase-8, fasl and caspase-3 increased significantly while the mRNA levels of bax, bcl2, apaf1 and caspase-9 remained unchanged. This result showed that increased stocking density caused splenic cell apoptosis, which were closely associated with the FasL signaling pathway. Our findings revealed that crowding stress could influence fish nonspecific immune response negatively and increase inappropriate apoptosis of the spleen, which would make fish more susceptible to pathogens and ultimately impair fish survival. The breeding density utilized in this study also provides some reference values in intensive aquaculture systems from the perspective of fish health and welfare.
Collapse
Affiliation(s)
- Wang Lin
- College of Fisheries, Huazhong Agricultural University, Wuhan 430070, PR China
| | - Li Li
- College of Fisheries, Huazhong Agricultural University, Wuhan 430070, PR China; Hubei Provincial Engineering Laboratory for Pond Aquaculture, Wuhan 430070, PR China; National Demonstration Center for Experimental Aquaculture Education, Huazhong Agricultural University, Wuhan 430070, PR China
| | - Jie Chen
- College of Fisheries, Huazhong Agricultural University, Wuhan 430070, PR China
| | - Dapeng Li
- College of Fisheries, Huazhong Agricultural University, Wuhan 430070, PR China; Hubei Provincial Engineering Laboratory for Pond Aquaculture, Wuhan 430070, PR China; National Demonstration Center for Experimental Aquaculture Education, Huazhong Agricultural University, Wuhan 430070, PR China
| | - Jie Hou
- College of Fisheries, Huazhong Agricultural University, Wuhan 430070, PR China
| | - Honghui Guo
- College of Fisheries, Huazhong Agricultural University, Wuhan 430070, PR China
| | - Jianzhong Shen
- College of Fisheries, Huazhong Agricultural University, Wuhan 430070, PR China.
| |
Collapse
|
|
23
|
Xu T, Kong Z, Zhao H. Relationship Between Tumor Necrosis Factor-α rs361525 Polymorphism and Gastric Cancer Risk: A Meta-Analysis. Front Physiol 2018; 9:469. [PMID: 29867530 PMCID: PMC5962813 DOI: 10.3389/fphys.2018.00469] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2018] [Accepted: 04/13/2018] [Indexed: 12/17/2022] Open
Abstract
Tumor necrosis factor (TNF)-α, a major part in inflammatory, infectious and tumor processes, and is pivotal at the early stages of gastric cancer. Relationship between its risk and TNF-α rs361525 polymorphism has been demonstrated, but remains conflicting and controversial. Therefore, a meta-analysis was conducted to more precisely estimate this relationship. PubMed, Web of Science, EMBASE and CNKI were comprehensively searched to find out relevant articles through October 5, 2017. The strength of the relationship was assessed using pooled odds ratios and 95% confidence intervals. Totally 20 articles were included involving 4,084 cases and 7,010 controls. No significant relationship between TNF-α rs361525 polymorphism and increased GC risk was found in the whole populations. Subgroup analyses uncovered TNF-α rs361525 polymorphism intensified the risk of GC among Asians under five models, but decreased the risk of GC among Caucasiansin the allelic and dominant models. Subgroup analysis by genotyping methods revealed increased risk for other methods. In conclusion, this meta-analysis suggests TNF-α rs361525 polymorphism is related to the risk of GC, especially for Asians.
Collapse
Affiliation(s)
- Tianshu Xu
- Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Zhijun Kong
- Department of General Surgery, Affiliated Hospital of Nanjing Medical University, Changzhou Second People's Hospital, Changzhou, China
| | - Hui Zhao
- Department of General Surgery, Wuxi Third People's Hospital, Wuxi, China
| |
Collapse
|
|
24
|
Sahami-Fard MH. Association between interleukin-10 -592 A/C polymorphism and gastrointestinal tract cancer risk: A meta-analysis. Int J Biol Markers 2018; 33:244-253. [PMID: 29720026 DOI: 10.1177/1724600817747525] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
BACKGROUND Recent evidence suggests that -592 A/C polymorphism in the interleukin-10 (IL-10) gene may influence risk of gastrointestinal tract cancer; however, individual studies have provided conflicting and inconclusive results. Therefore, this meta-analysis was conducted to assess the association between IL-10 -592 A/C polymorphism and gastrointestinal tract cancer susceptibility. METHODS EMBASE, PubMed, Web of Science, and China National Knowledge Infrastructure databases were searched for case-control studies published before 1 May 2017. A total of 36 studies involving 8069 cases and 13,089 controls were included in the present meta-analysis according to the inclusion criteria. The random- or fixed-effect model was utilized to calculate pooled odds ratio (OR) with 95% confidence interval (CI), and to survey the association. RESULTS By and large IL-10 -592 A/C (rs1800872) polymorphism was not associated with gastrointestinal cancer risk in five genetic models (A vs. C: OR 1.00; 95% CI 0.93, 1.08; POR = 0.960; AA vs. CC: OR 0.98; 95% CI 0.85, 1.14; POR = 0.835; CA vs. CC: OR 1.01; 95% CI 0.94, 1.08; POR = 0.776; AA+CA vs. CC: OR 1.03; 95% CI 0.94, 1.12; POR = 0.592; AA vs. CA+CC: OR 0.98; 95% CI 0.87, 1.10; POR = 0.666). Similar results were also achieved after stratification by the Hardy-Weinberg equilibrium, ethnicity, source of controls, and cancer type. CONCLUSION The results of this meta-analysis indicated that there is no association between the IL-10 -592 A/C promoter polymorphism and gastrointestinal tract cancer susceptibility.
Collapse
|
|
25
|
Genetics in TNF-TNFR pathway: A complex network causing spondyloarthritis and conditioning response to anti-TNFα therapy. PLoS One 2018; 13:e0194693. [PMID: 29579081 PMCID: PMC5868803 DOI: 10.1371/journal.pone.0194693] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2017] [Accepted: 03/07/2018] [Indexed: 12/20/2022] Open
Abstract
Objectives We investigated whether polymorphisms (SNPs) in the promoter region of TNFA, or in the autoinflammatory TNFRSF1A and MEFV genes, concur with HLA-B27 in enhancing the risk of Spondyloarthritis (SpA) and/or in predicting the response to anti-TNFα treatment. Methods 373 controls and 137 SpA (82 with Psoriatic Arthritis-PsA and 55 with Ankylosing Spondylitis- AS; 98/137 under TNFα inhibitor therapy) from the Veneto Region (Italy) were studied. TNFA polymorphisms (-1031T>C;-857C>T;-376G>A;-308G>A;-238G>A) and HLA-B27 were assayed by RT-PCR. Direct sequencing of MEFV (exons 2,3,5 and 10) and TNFRSF1A (exons 2,3,4 and 6) genes were performed. Results HLA-B27 was associated with AS (χ2 = 120.1; p = 0.000). Only the TNFA -1031T>C was singly associated with SpA, and the haplotype C/G, resulting from -1031T>C/-308G>A combination, was significantly associated with a reduced risk of SpA (OR: 0.67, CI: 0.46–0.97; p = 0.035). Two SNPs were identified in TNFRSF1A, the R92Q (Minor allele frequency-MAF = 0.034) and c.625+10A>G (MAF = 0.479). None of them was associated with SpA (p>0.05). The TNFRSF1A c.625+10 G allele was associated with late response to anti-TNFα therapy (p = 0.031). Twenty-one SNPs were identified in MEFV gene, 10 with a known potential functional significance. Variant alleles were extremely rare in our population (MAF<0.025) except for R202Q (MAF = 0.27). None was associated with SpA diagnosis (p>0.05). Conclusion TNFRSF1A and MEFV gene SNPs are not associated with SpA in the North-East of Italy. AS risk appears to depend not only on HLA-B27, but also on the protective TNFA haplotype -1031C/-308G. The TNFRSF1A c.625+10A>G impacts on the response to anti-TNFα therapy.
Collapse
|
|
26
|
Namazi A, Forat-Yazdi M, Jafari M, Farahnak S, Nasiri R, Foroughi E, Abolbaghaei SM, Neamatzadeh H. ASSOCIATION OF INTERLEUKIN-10 -1082 A/G (RS1800896) POLYMORPHISM WITH SUSCEPTIBILITY TO GASTRIC CANCER: META-ANALYSIS OF 6,101 CASES AND 8,557 CONTROLS. ARQUIVOS DE GASTROENTEROLOGIA 2018; 55:33-40. [PMID: 29561974 DOI: 10.1590/s0004-2803.201800000-18] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/05/2017] [Accepted: 09/11/2017] [Indexed: 02/08/2023]
Abstract
BACKGROUND The promoter -1082 A/G (rs1800896) polymorphism of Interleukin-10 (IL-10) gene have been widely reported and considered to have a significant role on gastric cancer risk, but the results are inconsistent. OBJECTIVE To clarify the association, we conducted a meta-analysis to investigate the associations IL-10 -1082 A/G polymorphism with gastric cancer. METHODS Eligible articles were identified by searching databases including PubMed, Web of Science, and Google Scholar up to August 03, 2017. Odds ratios (OR) with corresponding 95% confidence intervals (CIs) were used to assess the association. RESULTS A total of 30 case-control studies with 6,101 cases and 8,557 controls were included in this meta-analysis. Overall, a significant association between IL-10 -1082 A/G polymorphism and gastric cancer risk was observed under the allele model (G vs A: OR=1.305, 95% CI=1.076-1.584; P=0.007), heterozygote model and (GA vs AA: OR=1.252, 95% CI=1.252-1.054; P=0.011) and dominant model (GG+GA vs AA: OR=1.264, 95% CI=1.053-1.516; P=0.012). In the subgroup analysis by ethnicity, increased gastric cancer risk were found in Asians under the allele model (G vs A: OR=1.520, 95% CI=1.172-1.973; P=0.002), homozygote model (GG+GA vs AA: OR=1.571, 95% CI=1.023-2.414; P= 0.039), heterozygote model (GA vs AA: OR=1.465, 95% CI=1.192-1.801; P≤0.001) and dominant model (GG+GA vs AA: OR=1.448, 95% CI=1.152-1.821; P=0.002), but not among Caucasian and Latinos populations. CONCLUSION These results suggested that the IL-10 -1082 A/G (rs1800896) polymorphism might contribute to the gastric cancer susceptibility, especially among Asians.
Collapse
Affiliation(s)
- Abolfazl Namazi
- Department of Internal Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Mohammad Forat-Yazdi
- Department of Internal Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Mohammadali Jafari
- Department of Emergency Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Soudabeh Farahnak
- Department of Endodontic, Arak University of Medical Sciences, Arak, Iran
| | - Rezvan Nasiri
- Department of Pediatric Dentistry, Arak University of Medical Sciences, Arak, Iran
| | - Elnaz Foroughi
- Department of Restorative and Esthetic, Arak University of Medical Sciences, Arak, Iran
| | | | - Hossein Neamatzadeh
- Mother and Newborn Health Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| |
Collapse
|
|
27
|
Proinflammatory Cytokine IL-17 Shows a Significant Association with Helicobacter pylori Infection and Disease Severity. Gastroenterol Res Pract 2017; 2017:6265150. [PMID: 29391865 PMCID: PMC5748147 DOI: 10.1155/2017/6265150] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2017] [Revised: 10/11/2017] [Accepted: 10/29/2017] [Indexed: 01/18/2023] Open
Abstract
Background The pro- and anti-inflammatory cytokines play an important role in the immune response against H. pylori infection. The proinflammatory cytokines of Th17 cells have been suggested to play a major role in H. pylori infection and resulting gastric inflammation. Objective The objective of this study was to compare the expression of selected inflammatory cytokines (IL-10, IL-17, IL-21, IL-23, and TNF-α) in H. pylori-infected patients and healthy controls and to understand their association with H. pylori infection and disease severity. Results The expression levels of IL-17 and IL-23 were significantly higher in H. pylori-infected patients. The expression of IL-21 was also higher in H. pylori-positive patients but there was no significant association with infection. IL-17 expression showed a significant increase with the severity of chronic gastritis. Conclusion The proinflammatory cytokine, IL-17, shows a significant association with H. pylori infection and disease severity in a Sri Lankan dyspeptic patient population.
Collapse
|
|
28
|
Gross SA, Paustenbach DJ. Shanghai Health Study (2001-2009): What was learned about benzene health effects? Crit Rev Toxicol 2017; 48:217-251. [PMID: 29243948 DOI: 10.1080/10408444.2017.1401581] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
The Shanghai Health Study (SHS) was a large epidemiology study conducted as a joint effort between the University of Colorado and Fudan University in Shanghai, China. The study was funded by members of the American Petroleum Institute between 2001 and 2009 and was designed to evaluate the human health effects associated with benzene exposure. Two arms of the SHS included: an occupational-based molecular epidemiology study and several hospital-based case control studies. Consistent with historical literature, following sufficient exposure to relatively high airborne concentrations and years of exposure, the SHS concluded that exposure to benzene resulted in an increased risk of various blood and bone marrow abnormalities such as benzene poisoning, aplastic anemia (AA), myelodysplastic syndrome (MDS), and acute myeloid leukemia (AML). Non-Hodgkin lymphoma (NHL) was not significantly increased for the exposures examined in this study. Perhaps the most important contribution of the SHS was furthering our understanding of the mechanism of benzene-induced bone marrow toxicity and the importance of identifying the proper subset of MDS relevant to benzene. Investigators found that benzene-exposed workers exhibited bone marrow morphology consistent with an immune-mediated inflammatory response. Contrary to historic reports, no consistent pattern of cytogenetic abnormalities was identified in these workers. Taken together, findings from SHS provided evidence that the mechanism for benzene-induced bone marrow damage was not initiated by chromosome abnormalities. Instead, chronic inflammation, followed by an immune-mediated response, is likely to play a more significant role in benzene-induced disease initiation and progression than previously thought.
Collapse
|
|
29
|
Mărginean MO, Mărginean CO, Meliţ LE, Voidăzan S, Moldovan V, Bănescu C. The impact of host's genetic susceptibility on Helicobacter pylori infection in children. Medicine (Baltimore) 2017; 96:e7612. [PMID: 28746216 PMCID: PMC5627842 DOI: 10.1097/md.0000000000007612] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
The aim of our study was to investigate the impact of interleukin (IL)-6 190C/T, IL-6 174G/C, IL-6 572G/C, tumor necrosis factor-alpha (TNF-α) 308G/A, and angiotensin-converting enzyme (ACE) I/D gene polymorphisms on Helicobacter pylori (H. pylori) infection in children.A cross-sectional study was performed on 126 children (57 children with H. pylori infection and 69 children without H. pylori infection) aged between 3 and 18 years presenting to a Pediatrics Tertiary Hospital from Romania. Children were assessed clinically, endoscopically, histopathologically, and genetically.In our study, we found that the presence of the CT and CT+TT genotypes of IL-6 190C/T (P < .002 and P = .04), allele G of IL-6 572 G/C polymorphism (P = .01), genotypes GA and AA of TNF-α 308 G/A polymorphism (P = .04, P = .01), and genotype II of ACE I/D polymorphism (P = .02) were associated with H. pylori infection, while the CC genotype of IL-6 174G/C polymorphism was scarcely encountered in children with H. pylori infection [P = .02, odds ratio (OR) = 0.06; 95% confidence interval (95% CI): 0.003-0.128]. Taking under consideration the 4 variant genotypes (IL-6 572G/C, IL-6 190C/T, TNF-α 308G/A, and ACE I/D), we noticed a 2 times higher incidence of H. pylori infection (OR = 6.34; 95% CI: 2.15-25.8).We may consider that the IL-6 190C/T, IL-6 174G/C, IL-6 572G/C, TNF-α 308G/A, and ACE I/D gene polymorphisms may increase the children's susceptibility for acquiring H. pylori infection; therefore, they may contribute to the pathogenesis of H. pylori gastritis.
Collapse
Affiliation(s)
| | | | - Lorena Elena Meliţ
- Department of Pediatrics, University of Medicine and Pharmacy Tîrgu Mureş
| | - Septimiu Voidăzan
- Department of Epidemiology, University of Medicine and Pharmacy Tîrgu Mureş
| | - Valeriu Moldovan
- Genetics Laboratory, Center for Advanced Medical and Pharmaceutical Research, University of Medicine and Pharmacy Tîrgu Mureş, Romania
| | - Claudia Bănescu
- Genetics Laboratory, Center for Advanced Medical and Pharmaceutical Research, University of Medicine and Pharmacy Tîrgu Mureş, Romania
| |
Collapse
|
|
30
|
Zheng W, Zhang S, Zhang S, Min L, Wang Y, Xie J, Hou Y, Tian X, Cheng J, Liu K, Xu D, Yu X, Liu Z, Lv Y, Liang N, Zhang J, Liu F, Tian Y. The relationship between tumor necrosis factor-α polymorphisms and gastric cancer risk: An updated meta-analysis. Biomed Rep 2017; 7:133-142. [PMID: 28804625 PMCID: PMC5526040 DOI: 10.3892/br.2017.934] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2017] [Accepted: 06/21/2017] [Indexed: 12/13/2022] Open
Abstract
The aim of the present study was to evaluate the relationship between tumor necrosis factor-α (TNF-α) and the development of gastric cancer, and to investigate whether it can be used as a biological marker for gastric cancer. In the current study, a new meta-analysis was performed to assess the association between TNF-α gene polymorphisms and gastric cancer susceptibility. Subgroup analyses based on ethnicity, control population source and non-cardia cancers were also conducted. Summary odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random-effects model. TNF-α 308 polymorphisms indicated a significant relationship with gastric cancer risk among a normal population [GA/AA vs. GG; 1.17 (1.10–1.23)]. In analysis stratified by ethnicity, TNF-α 238 displayed an association with gastric cancer risk in eastern populations [GA/AA vs. GG: 1.24 (1.02–1.50)], but not in western populations [GA/AA vs. GG: 0.96 (0.79–1.18)]. The overall ORs (95% CIs) for TNF-α 857, TNF-α 1031 and TNF-α 863 were 1.13 (1.04–1.24), 0.94 (0.85–1.05) and 0.89 (0.78–1.02), respectively, under dominant genetic model comparison. Among the above three SNPs, only TNF-α 857 was robustly associated with gastric cancer inclination, and this association remained consistently robust when limited to non-cardia gastric cancers [GA/AA vs. GG: 1.16 (1.03–1.31)]. TNF-α 308 and TNF-α 857 genotypes were potential risk factors of statistical significance in gastric cancer, and TNF-α 238 indicated to be significantly associated with gastric cancer risk only in eastern populations. TNF-α 1031 and TNF-α 863 were not significantly associated with gastric cancer risk.
Collapse
Affiliation(s)
- Wenxian Zheng
- Department of Oncology, Shanghai Jiaotong University Affiliated Sixth People Hospital, Shanghai 200233, P.R. China
| | - Shuisheng Zhang
- Department of Abdominal Surgical Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China
| | - Shenfeng Zhang
- Department of Oncology, Zaozhuang Municipal Hospital of Shandong Province, Zaozhuang, Shandong 277101, P.R. China
| | - Li Min
- Department of Gastroenterology, Beijing Medical University, National Clinical Center for Digestive Disease Center, Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing 100050, P.R. China
| | - Yihong Wang
- Department of Radiation Oncology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China
| | - Jian Xie
- Department of Radiation Oncology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China
| | - Yong Hou
- Department of Radiation Oncology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China
| | - Xiufang Tian
- Department of Radiation Oncology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China
| | - Jian Cheng
- Department of Radiation Oncology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China
| | - Kun Liu
- Department of Radiation Oncology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China
| | - Deguo Xu
- Department of Radiation Oncology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China
| | - Xinshuang Yu
- Department of Radiation Oncology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China
| | - Zhen Liu
- Department of Radiation Oncology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China
| | - Yajuan Lv
- Department of Radiation Oncology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China
| | - Ning Liang
- Department of Radiation Oncology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China
| | - Jiandong Zhang
- Department of Radiation Oncology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China
| | - Fengjun Liu
- Department of Radiation Oncology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China
| | - Yuan Tian
- Department of Radiation Oncology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China
| |
Collapse
|
|
31
|
Polymorphisms and haplotypes of the interleukin 2 gene are associated with an increased risk of gastric cancer. The possible involvement of Helicobacter pylori. Cytokine 2017; 96:203-207. [PMID: 28458166 DOI: 10.1016/j.cyto.2017.04.020] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2016] [Revised: 04/19/2017] [Accepted: 04/20/2017] [Indexed: 12/11/2022]
Abstract
Interleukin 2 (IL-2) is a pro-inflammatory cytokine that is mainly synthesized by immunoregulatory T helper cells and which plays an important role in antitumor immunity. Helicobacter pylori (H. pylori) is a gram-negative bacterium that colonizes the gastric mucosa and induces the production of IL-2. This process increases the magnitude of inflammation and may influence the development of gastric pathologies. In light of the possible involvement of IL-2 and the presence of H. pylori in gastric diseases, this study investigated possible associations between the IL-2 polymorphisms +114 T>G (rs2069763) and -330 T>G (rs2069762) and the development of gastric cancer; these associations were then correlated with the presence of H. pylori. Gastric biopsies were obtained from 294 dyspeptic patients (173♀/123♂). Of these samples, 181 were chronic gastritis samples (102♀/79), 62 were samples of intact gastric mucosa (47♀/15♂), and 51 were samples of gastric cancer (22♀/29♂). PCR-RFLP was used to characterize the +114 T>G and -330 T>G polymorphisms. Considering the genetic characteristics of the study population and based on the codominant model, a high risk of gastric cancer among patients with normal gastric tissue and patients with gastric cancer was found in subjects with the IL-2-330 GG genotype (OR=6.43, 95% CI: 1.47-28.10, p=0.044). The data was adjusted for the presence of H. pylori. Among patients with gastritis and patients with gastric cancer, a high risk was found among subjects with the IL-2-330 GG genotype (OR=4.47, 95% CI: 1.84-10.84, p=0.0022). When the IL-2 +114 polymorphism was analyzed, similar results were found. Among the patients with normal gastric tissue and the patients with gastric cancer, subjects carrying the +114 TT genotype were found to be at a high risk of gastric cancer (OR=5.97, 95% CI: 1.60-22.27, p=0.013). This data was also adjusted for the presence of H. pylori. Among patients with gastritis and patients with gastric cancer, a high risk was found in subjects carrying the +114 TT genotype (OR=6.36, 95% CI: 2.66-15.21, p<0.0001). The haplotype was also analyzed. The -330G/+114T haplotype was found to be significantly associated with gastric cancer. Therefore, our results show that, among patients with H. pylori infection, the -330 GG and +114 TT genotypes are significantly associated with a high risk of developing gastric cancer, as is the -330G/+114T haplotype.
Collapse
|
|
32
|
Tumor Necrosis Factor- α T-857C (rs1799724) Polymorphism and Risk of Cancers: A Meta-Analysis. DISEASE MARKERS 2016; 2016:4580323. [PMID: 28115787 PMCID: PMC5223007 DOI: 10.1155/2016/4580323] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/06/2016] [Revised: 12/04/2016] [Accepted: 12/06/2016] [Indexed: 01/08/2023]
Abstract
Objectives. To investigate the potential association of tumor necrosis factor-α T-857C polymorphism with susceptibility to the five common malignant tumors. Materials and Methods. A comprehensive search of PubMed/Medline, Embase, and Web of Science databases was performed up to November 2015. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to assess the strength of the association. Subgroup analysis, heterogeneity analyses, and publication bias were also texted in the meta-analysis. Results. A total of twenty-two publications involving 5215 cases and 6755 controls were recruited. Overall, the meta-analysis revealed an increased risk between the TNF-α T-857C polymorphism and gastric cancer susceptibility in T versus C model, heterozygote genetic model, and dominant genetic model. An increased risk between the TNF-α T-857C polymorphism and hepatocellular cancer susceptibility in homozygote genetic model and recessive genetic model was also found. No significant association was found between the TNF-α T-857C polymorphism and colorectal cancer, cervical cancer, and prostate cancer. Conclusions. Our meta-analyses suggest that TNF-α T-857C polymorphism may be associated with increased risk of gastric cancer and hepatocellular cancer development. Therefore, the TNF-α T-857C polymorphism could be considered as one possible risk factor of gastric cancer and hepatocellular cancer according to our study.
Collapse
|
|
33
|
Jemli A, Eshili A, Trifa F, Mechri A, Zaafrane F, Gaha L, Juckel G, Tensaout BBHJ. Association of the IFN-γ (+874A/T) Genetic Polymorphism with Paranoid Schizophrenia in Tunisian Population. Immunol Invest 2016; 46:159-171. [PMID: 27819519 DOI: 10.1080/08820139.2016.1237523] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
Since growing evidence suggests a significant role of chronic low-grade inflammation in the physiopathology of schizophrenia, we have hypothesized that functional genetic variant of the IFN gamma (IFN-γ; +874A/T; rs2430561) gene may be involved in the predisposition to schizophrenia. This research is based on a case-control study which aims to identify whether polymorphism of the IFN-γ gene is a risk factor for the development of schizophrenia. The RFLP-PCR genotyping of the IFN-γ gene was conducted on a Tunisian population composed of 218 patients and 162 controls. The IFN-γ (+874A/T) polymorphism analysis showed higher frequencies of minor homozygous genotype (TT) and allele (T) in all patients compared with controls (11.5 vs. 4.9%; p = 0.03, OR = 2.64 and 30.7 vs. 24.1%, p = 0.04, OR = 1.4, respectively). This correlation was confirmed for male but not for female patients. Also, the T allele was significantly more common among patients with paranoid schizophrenia when compared with controls (25.8 vs. 4.9%, p = 0.0001; OR = 6.7). Using the binary regression analysis to eliminate confounding factors as age and sex, only this last association remained significant (p = 0.03; OR = 1.76, CI = 1.05-2.93). In conclusion, our results showed a significant association between +874A/T polymorphism of IFN-γ and paranoid schizophrenia, suggesting that this single nucleotide polymorphism (SNP) or another at proximity could predispose to paranoid schizophrenia. Since the minor allele of this polymorphism was correlated with an increased expression of their product, our study validates the hypothesis of excessive pro-inflammatory cytokine in the physiopathology of paranoid schizophrenia.
Collapse
Affiliation(s)
- Achraf Jemli
- a Laboratory of Genetics, Biodiversity and Bioresource Valorization, Higher Institute of Biotechnology of Monastir , University of Monastir , Monastir , Tunisia
| | - Awatef Eshili
- a Laboratory of Genetics, Biodiversity and Bioresource Valorization, Higher Institute of Biotechnology of Monastir , University of Monastir , Monastir , Tunisia
| | - Fatma Trifa
- b Department of Biostatistics , Higher Institute of Biotechnology of Monastir, University of Monastir , Monastir , Tunisia.,c Laboratory of Biomass Valorization and Production of Eucaryotic Proteins, Center of Biotechnology of Sfax , Sfax , Tunisia
| | - Anouar Mechri
- d Department of Psychiatry and Vulnerability to Psychoses Laboratory - CHU Monastir , University of Monastir , Monastir , Tunisia
| | - Ferid Zaafrane
- d Department of Psychiatry and Vulnerability to Psychoses Laboratory - CHU Monastir , University of Monastir , Monastir , Tunisia
| | - Lotfi Gaha
- d Department of Psychiatry and Vulnerability to Psychoses Laboratory - CHU Monastir , University of Monastir , Monastir , Tunisia
| | - George Juckel
- e Department of Psychiatry and Psychotherapy , Ruhr University, Bochum LWL University Hospital Bochum , Bochum , Germany
| | - Besma Bel Hadj Jrad Tensaout
- a Laboratory of Genetics, Biodiversity and Bioresource Valorization, Higher Institute of Biotechnology of Monastir , University of Monastir , Monastir , Tunisia
| |
Collapse
|
|
34
|
Hu Y, Liu JP, Zhu Y, Lu NH. The Importance of Toll-like Receptors in NF-κB Signaling Pathway Activation by Helicobacter pylori Infection and the Regulators of this Response. Helicobacter 2016; 21:428-40. [PMID: 26763943 DOI: 10.1111/hel.12292] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Helicobacter pylori (H. pylori) is a common pathogenic bacterium in the stomach that infects almost half of the population worldwide and is closely related to gastric diseases and some extragastric diseases, including iron-deficiency anemia and idiopathic thrombocytopenic purpura. Both the Maastricht IV/Florence consensus report and the Kyoto global consensus report have proposed the eradication of H. pylori to prevent gastric cancer as H.pylori has been shown to be a major cause of gastric carcinogenesis. The interactions between H. pylori and host receptors induce the release of the proinflammatory cytokines by activating proinflammatory signaling pathways such as nuclear factor kappa B (NF-κB), which plays a central role in inflammation, immune response, and carcinogenesis. Among these receptors, Toll-like receptors (TLRs) are classical pattern recognition receptors in the recognition of H. pylori and the mediation of the host inflammatory and immune responses to H. pylori. TLR polymorphisms also contribute to the clinical consequences of H. pylori infection. In this review, we focus on the functions of TLRs in the NF-κB signaling pathway activated by H. pylori, the regulators modulating this response, and the functions of TLR polymorphisms in H.pylori-related diseases.
Collapse
Affiliation(s)
- Yi Hu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Jian-Ping Liu
- Department of Biosciences and Nutrition, Karolinska Institute, Huddinge, Sweden
| | - Yin Zhu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
| | - Nong-Hua Lu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
| |
Collapse
|
|
35
|
Mahmoud AA, Sheneef A, Goda AM, Ismail MA, Abualfadl EM. Association of interferon-γ and its (+874 T/A) gene polymorphism with type 2 diabetes mellitus in rheumatoid arthritis patients. THE EGYPTIAN RHEUMATOLOGIST 2016. [DOI: 10.1016/j.ejr.2015.09.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
|
|
36
|
Cui X, Huang Q, Li X, Liu F, Wang D, Yan D, Wang B, Yang C, Mi J, Tian G. Relationship Between Interleukin-10 Gene C-819T Polymorphism and Gastric Cancer Risk: Insights From a Meta-Analysis. MEDICAL SCIENCE MONITOR : INTERNATIONAL MEDICAL JOURNAL OF EXPERIMENTAL AND CLINICAL RESEARCH 2016; 22:2839-45. [PMID: 27516059 PMCID: PMC4993219 DOI: 10.12659/msm.895333] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
BACKGROUND As a pleiotropic cytokine, interleukin-10 (IL-10) plays a regulatory role in carcinogenesis and tumor growth. The aim of this meta-analysis was to assess the susceptibility of the IL-10 gene C-819T polymorphism to gastric cancer. MATERIAL AND METHODS Study identification and data extraction were independently completed by 2 authors. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated and summarized. RESULTS In total, 11 articles including 1960 gastric cancer patients and 3705 controls were qualified. Overall analyses revealed a 13% reduced risk of gastric cancer conferred by the -819T allele relative to the -819C allele (OR=0.87; 95% CI: 0.77-0.97; P=0.016), without heterogeneity (I2=35.1%). In subgroup analyses, a significant difference was identified in East Asian populations (OR=0.85; 95% CI: 0.73-0.98; P=0.029, I2=43.6%), for gastric adenocarcinoma (OR=0.80; 95% CI: 0.66-0.96; P=0.017, I2=0.0%), and in population-based studies (OR=0.81; 95% CI: 0.70-0.93; P=0.003, I2=0.0%). The visual funnel plots and Egger's tests suggested no evidence of publication bias. CONCLUSIONS Extending previous findings, we demonstrate a protective role of the IL-10 gene -819T allele in susceptibility to gastric cancer, and this role was more evident for gastric adenocarcinoma.
Collapse
Affiliation(s)
- Xigang Cui
- Department of Gastric and Intestine, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong, China (mainland)
| | - Qingxian Huang
- Department of Gastric and Intestine, Yantai Yuhuangding Hospital, Yantai, Shandong, China (mainland)
| | | | - Fang Liu
- Medicine and Pharmacy Research Center, Binzhou Medical University, Yantai, Shandong, China (mainland)
| | - Dan Wang
- Medicine and Pharmacy Research Center, Binzhou Medical University, Yantai, Shandong, China (mainland)
| | - Dong Yan
- Medicine and Pharmacy Research Center, Binzhou Medical University, Yantai, Shandong, China (mainland)
| | - Bin Wang
- Institute of Molecular Imaging, Binzhou Medical University, Yantai, Shandong, China (mainland)
| | - Chunhua Yang
- Medicine and Pharmacy Research Center, Binzhou Medical University, Yantai, Shandong, China (mainland)
| | - Jia Mi
- Medicine and Pharmacy Research Center, Binzhou Medical University, Yantai, Shandong, China (mainland)
| | - Geng Tian
- Medicine and Pharmacy Research Center, Binzhou Medical University, Yantai, Shandong, China (mainland)
| |
Collapse
|
|
37
|
Jia ZF, Zhang SL, Cao XY, Zhou BS, Jiang J. Interaction between Helicobacter pylori and host genetic variants in gastric carcinogenesis. Future Oncol 2016; 12:2127-34. [PMID: 27324311 DOI: 10.2217/fon-2016-0233] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Helicobacter pylori (H. pylori) is the definite carcinogen of gastric cancer. H. pylori infection induces chronic inflammation, causes DNA damage and aberrant methylation of genes and these pathways are involved in H. pylori-related gastric carcinogenesis. Polymorphisms of the genes involved in these pathways could alter susceptibility to gastric cancer. In this mini review, we focused on the role of polymorphisms in these genes on the susceptibility to gastric cancer, with a particular emphasis on their possible interactions with H. pylori infection. We found that many studies on this theme did not simultaneously report H. pylori infection and the interactions remained inconclusive.
Collapse
Affiliation(s)
- Zhi-Fang Jia
- Division of Clinical Research, First Hospital of Jilin University, Changchun 130021, China.,Department of Epidemiology, School of Public Health, China Medical University, Shenyang 110112, China
| | - Song-Ling Zhang
- Department of Gynecological Oncology, First Hospital of Jilin University, Changchun 130021, China
| | - Xue-Yuan Cao
- Department of Gastrointestinal Surgery, First Hospital of Jilin University, Changchun 130021, China
| | - Bao-Sen Zhou
- Department of Epidemiology, School of Public Health, China Medical University, Shenyang 110112, China
| | - Jing Jiang
- Division of Clinical Research, First Hospital of Jilin University, Changchun 130021, China
| |
Collapse
|
|
38
|
Abu EK, Boampong JN, Kyei S, Afoakwah R, Ayi I. Associations between Polymorphisms within Interferon Gamma and Tumor Necrosis Factor Genes and Toxoplasma Retinochoroiditis in Ghanaian Patients. Ocul Immunol Inflamm 2016; 25:678-684. [DOI: 10.3109/09273948.2016.1159315] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Affiliation(s)
- Emmanuel Kwasi Abu
- Department of Optometry, School of Allied Health Sciences, University of Cape Coast, Ghana
- Department of Biomedical and Forensic Sciences, School of Allied Health Sciences, University of Cape Coast, Ghana
| | - Johnson N. Boampong
- Department of Biomedical and Forensic Sciences, School of Allied Health Sciences, University of Cape Coast, Ghana
| | - Samuel Kyei
- Department of Optometry, School of Allied Health Sciences, University of Cape Coast, Ghana
| | - Richmond Afoakwah
- Department of Biomedical and Forensic Sciences, School of Allied Health Sciences, University of Cape Coast, Ghana
| | - Irene Ayi
- Department of Parasitology, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Ghana
| |
Collapse
|
|
39
|
Sałagacka-Kubiak A, Zebrowska M, Jeleń A, Mirowski M, Balcerczak E. Assessment of TNFA polymorphisms at positions -857 and -863 in Polish peptic ulcer patients. Adv Med Sci 2016; 61:164-8. [PMID: 26774268 DOI: 10.1016/j.advms.2015.12.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2014] [Revised: 10/28/2015] [Accepted: 12/01/2015] [Indexed: 11/28/2022]
Abstract
PURPOSE Peptic ulceration connected with chronic inflammation in gastrointestinal mucosa could be induced by Helicobacter pylori infection. Tumor necrosis factor alpha (TNF-α) encoded by TNFA gene is a key mediator in the inflammation process. There are several polymorphisms in the promoter of TNFA influencing its transcriptional activity. -857C>T (rs1799724) and -863C>A (rs1800630) substitutions may be responsible for increased TNFA transcription and TNF-α production. The association of these two polymorphisms with peptic ulceration and the development of H. pylori infection in peptic ulcer patients in Poles were evaluated. MATERIAL AND METHODS Polymorphisms were assessed by PCR-RFLP in 203 peptic ulcer patients. H. pylori infection was confirmed by rapid urease test. The results of genotyping were compared with those obtained for 248 healthy Polish individuals. RESULTS There were no significant differences in genotype and allele frequencies for both investigated polymorphisms between peptic ulcer patients and healthy individuals. No associations between frequencies of particular genotypes and alleles for both SNPs and the presence of H. pylori infection in peptic ulcer patients and in subgroups of peptic ulcer women and men were confirmed. CONCLUSIONS The investigated SNPs are not risk factors for peptic ulcer development. They are not risk factors for H. pylori infection in ulcer patients.
Collapse
Affiliation(s)
- Aleksandra Sałagacka-Kubiak
- Laboratory of Molecular Diagnostics and Pharmacogenomics, Department of Pharmaceutical Biochemistry and Molecular Diagnostics, Medical University of Lodz, Łódź, Poland
| | - Marta Zebrowska
- Laboratory of Molecular Diagnostics and Pharmacogenomics, Department of Pharmaceutical Biochemistry and Molecular Diagnostics, Medical University of Lodz, Łódź, Poland
| | - Agnieszka Jeleń
- Laboratory of Molecular Diagnostics and Pharmacogenomics, Department of Pharmaceutical Biochemistry and Molecular Diagnostics, Medical University of Lodz, Łódź, Poland
| | - Marek Mirowski
- Laboratory of Molecular Diagnostics and Pharmacogenomics, Department of Pharmaceutical Biochemistry and Molecular Diagnostics, Medical University of Lodz, Łódź, Poland
| | - Ewa Balcerczak
- Laboratory of Molecular Diagnostics and Pharmacogenomics, Department of Pharmaceutical Biochemistry and Molecular Diagnostics, Medical University of Lodz, Łódź, Poland.
| |
Collapse
|
|
40
|
Müller M, Hermann PC, Liebau S, Weidgang C, Seufferlein T, Kleger A, Perkhofer L. The role of pluripotency factors to drive stemness in gastrointestinal cancer. Stem Cell Res 2016; 16:349-57. [PMID: 26896855 DOI: 10.1016/j.scr.2016.02.005] [Citation(s) in RCA: 70] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2015] [Revised: 01/19/2016] [Accepted: 02/01/2016] [Indexed: 12/28/2022] Open
Abstract
A better molecular understanding of gastrointestinal cancers arising either from the stomach, the pancreas, the intestine, or the liver has led to the identification of a variety of potential new molecular therapeutic targets. However, in most cases surgery remains the only curative option. The intratumoral cellular heterogeneity of cancer stem cells, bulk tumor cells, and stromal cells further limits straightforward targeting approaches. Accumulating evidence reveals an intimate link between embryonic development, stem cells, and cancer formation. In line, a growing number of oncofetal proteins are found to play common roles within these processes. Cancer stem cells share features with true stem cells by having the capacity to self-renew in a de-differentiated state, to generate heterogeneous types of differentiated progeny, and to give rise to the bulk tumor. Further, various studies identified genes in cancer stem cells, which were previously shown to regulate the pluripotency circuitry, particularly the so-called "Yamanaka-Factors" (OCT4, KLF4, SOX2, and c-MYC). However, the true stemness potential of cancer stem cells and the role and expression pattern of such pluripotency genes in various tumor cell types remain to be explored. Here, we summarize recent findings and discuss the potential mechanisms involved, and link them to clinical significance with a particular focus on gastrointestinal cancers.
Collapse
Affiliation(s)
- Martin Müller
- Department of Internal Medicine I, Ulm University, Ulm, Germany
| | | | - Stefan Liebau
- Institute of Neuroanatomy, Eberhard Karls University Tuebingen, Tuebingen, Germany
| | - Clair Weidgang
- Department of Anesthesiology, Ulm University Hospital, Ulm, Germany
| | | | - Alexander Kleger
- Department of Internal Medicine I, Ulm University, Ulm, Germany.
| | - Lukas Perkhofer
- Department of Internal Medicine I, Ulm University, Ulm, Germany
| |
Collapse
|
|
41
|
Niu W, Pang Q, Lin T, Wang Z, Zhang J, Tai M, Zhang L, Zhang L, Gu M, Liu C, Qu K. A Causal Role of Genetically Elevated Circulating Interleukin-10 in the Development of Digestive Cancers: Evidence from Mendelian Randomization Analysis Based on 29,307 Subjects. Medicine (Baltimore) 2016; 95:e2799. [PMID: 26886630 PMCID: PMC4998630 DOI: 10.1097/md.0000000000002799] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Recent studies have observed a high level of circulating interleukin-10 (IL-10) in patients with digestive cancers, yet whether elevated IL-10 is causally associated with digestive cancers so far remained unresolved. We therefore meta-analyzed available observational studies with Mendelian randomization method to explore this causal association by employing IL-10 gene 3 variants (-592C>A, -819C>T, and -1082A>G) as instruments. Data were available from 52 articles encompassing 29,307 subjects. Subgroup analysis by cancer type indicated that -1082A>G was associated with increased risk of gastric cancer (odds ratio [OR] = 1.19; 95% confidence interval [CI]: 1.05-1.35; P = 0.006), and the association was reinforced for intestinal type gastric cancer (OR = 1.26; 95%CI: 1.09-1.44; P = 0.001). By ethnicity, risk estimate for -1082G allele carriers was increased by 21% for digestive cancers in East Asians (95%CI: 1.05-1.40; P = 0.009). As for the genotype-phenotype association, carriers of -1082G allele had an overall 20.21 pg/mL higher IL-10 level than those with -1082AA genotype (P = 0.023). In further Mendelian randomization analysis, the predicted OR for 10 pg/mL increment in IL-10 was 1.14 (95%CI: 1.01-16.99) in gastric cancer. Our findings provided evidence for a causal role of genetically elevated IL-10 in the development of gastric cancer, especially in East Asians and for intestinal type gastric cancer.
Collapse
Affiliation(s)
- Wenquan Niu
- From the State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (WN); Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province (QP, TL, ZW, JZ, MT, LZ, CL, KQ); Department of Hepatobiliary Surgery, The Affiliated Hospital of Qinghai University, Xining, Qinghai (ZW, LZ); Department of Ultrasound Diagnostics, The First Affiliated Hospital of Xi'an Jiaotong University (MT); Department of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province (LZ); and Chinese Academy of Sciences Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics (MG), Chinese Academy of Sciences, Beijing, China
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
42
|
Sun X, Xu Y, Wang L, Zhang F, Zhang J, Fu X, Jing T, Han J. Association between TNFA Gene Polymorphisms and Helicobacter pylori Infection: A Meta-Analysis. PLoS One 2016; 11:e0147410. [PMID: 26815578 PMCID: PMC4729674 DOI: 10.1371/journal.pone.0147410] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2015] [Accepted: 01/04/2016] [Indexed: 12/18/2022] Open
Abstract
Background Several host genetic factors are thought to affect susceptibility to Helicobacter pylori infection-related diseases, including tumor necrosis factor (TNF)-α. Previous studies have evaluated the association between TNFA gene polymorphisms and H. pylori infection, but the results were inconclusive. We conducted this meta-analysis to clarify the association between TNFA polymorphisms and H. pylori infection. Methods Published literature within PubMed, Embase, and the Cochrane Library were used in our meta-analysis. Data were analyzed with the Stata13.1 software package using pooled odds ratios (ORs) with 95% confidence intervals (CI). Results A total of 24 studies were included in our study. The TNFA -308G>A polymorphism was associated with decreasing H. pylori infection (AA vs. AG+GG, OR = 0.64, 95% CI = 0.43–0.97; AA vs. GG, OR = 0.64, 95% CI = 0.43–0.97). A significantly decreased risk was also found for -1031T>C polymorphism (CC vs. CT+TT, OR = 0.61, 95% CI = 0.44–0.84). -863C>A polymorphism was associated with increasing risk of H. pylori infection (AA+AC vs. CC, OR = 1.47, 95% CI = 1.16–1.86; A allele vs. C allele, OR = 1.40, 95% CI = 1.14–1.72). There was no significant association between -857C>T polymorphism and H. pylori infection. When stratified analysis was conducted on H. pylori infection detection methods, -857C>T and -863C>A polymorphisms were associated with H. pylori infection for the non-ELISA subgroup. When stratified for ethnicity or study design, -863C>A significantly increased the risk and -1031T>C decreased the risk for the Asian subgroup and hospital-based subgroup. Conclusion Results of our meta-analysis demonstrate that TNFA -308G>A and -1031 T>C polymorphisms may be protective factors against H. pylori infection, and -863C>A may be a risk factor, especially in Asian populations. Further studies with larger sample sizes are required to validate these results.
Collapse
Affiliation(s)
- Xudong Sun
- Department of Pathogenic Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China
| | - Yuanyuan Xu
- Department of Pathogenic Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China
| | - Li Wang
- Department of Pathogenic Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China
| | - Fuhua Zhang
- Department of Gastroenterology, Second Hospital of Gansu Province, Lanzhou, China
| | - Jinhua Zhang
- Department of Gastroenterology, Second Hospital of Gansu Province, Lanzhou, China
| | - Ximei Fu
- Department of Pathogenic Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China
| | - Tao Jing
- Department of Pathogenic Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China
| | - Jian Han
- Department of Pathogenic Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China
- * E-mail:
| |
Collapse
|
|
43
|
Zabaglia LM, Ferraz MA, Pereira WN, Orcini WA, de Labio RW, Neto AC, Wisnieski F, de Oliveira JG, de Arruda Cardoso Smith M, Payão SLM, Rasmussen LT. Lack of association among TNF-α gene expression, -308 polymorphism (G > A) and virulence markers of Helicobacter pylori. J Venom Anim Toxins Incl Trop Dis 2015; 21:54. [PMID: 26719751 PMCID: PMC4696262 DOI: 10.1186/s40409-015-0054-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2015] [Accepted: 12/21/2015] [Indexed: 12/18/2022] Open
Abstract
Background Tumor necrosis factor plays a critical role in the pathogenesis of gastric diseases such as gastric cancer, and an abnormal inflammatory response has frequently been observed in dyspeptic patients. Helicobacter pylori infection can induce a gastric mucosal inflammatory response that may be influenced by -308 (G > A) polymorphisms and gene expression of the TNF-α gene. Methods One hundred and thirty-four gastric biopsy samples were collected from patients of both genders (61♂ and 73♀, mean age 40.3 ± 24.2 years) with gastric symptoms. The -308 (G > A) polymorphism of TNF-α was characterized using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). The expression level was measured using real-time PCR, and relative quantification (RQ) was calculated using the comparative CT method (2-ΔΔCT). Results The analysis revealed an increase in TNF-α gene expression in patients with gastritis; on the other hand, no statistical differences were observed in patients with gastric cancer. In addition, no association was found among -308 polymorphism genotypes, virulence markers, or TNF-α gene expression. Conclusions Helicobacter pylori induces a large increase in TNF-α expression in patients with gastritis, regardless of tissue inflammation, but after the tissue becomes neoplastic, the presence of bacteria did not influence expression. These results suggest that the TNF-α pathway may play an important role in the progression from gastritis to gastric cancer
Collapse
Affiliation(s)
- Luanna Munhoz Zabaglia
- Universidade Sagrado Coração, Rua Irmã Arminda 10-50, Jardim Brasil, CEP 17011-160 Bauru, SP Brazil
| | - Mariane Avante Ferraz
- Universidade Sagrado Coração, Rua Irmã Arminda 10-50, Jardim Brasil, CEP 17011-160 Bauru, SP Brazil
| | - Weendelly Nayara Pereira
- Universidade Sagrado Coração, Rua Irmã Arminda 10-50, Jardim Brasil, CEP 17011-160 Bauru, SP Brazil
| | - Wilson Aparecido Orcini
- Universidade Sagrado Coração, Rua Irmã Arminda 10-50, Jardim Brasil, CEP 17011-160 Bauru, SP Brazil
| | | | | | - Fernanda Wisnieski
- Universidade Federal de São Paulo, Rua Sena Madureira, 1500, 04021-001 São Paulo, SP Brazil
| | | | | | - Spencer Luiz Marques Payão
- Universidade Sagrado Coração, Rua Irmã Arminda 10-50, Jardim Brasil, CEP 17011-160 Bauru, SP Brazil ; Faculdade de Medicina de Marília, Rua Lourival Freire 240, 17519-050 Marília, SP Brazil
| | | |
Collapse
|
|
44
|
Stubljar D, Skvarc M. Helicobacter pylori vs immune system or antibiotics. World J Immunol 2015; 5:142-151. [DOI: 10.5411/wji.v5.i3.142] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2015] [Revised: 06/18/2015] [Accepted: 07/27/2015] [Indexed: 02/05/2023] Open
Abstract
Helicobacter pylori (H. pylori) infection has often no clinical signs and is one of the most common bacterial infections. All infected subjects have histology of active chronic gastritis. In some cases patients develop peptic ulcer and minority of them develop gastric cancer. Gastric cancer is multifactorial disease, thus various progressions of H. pylori infection and disease are dependent on the host genetic factors, the characteristics of the individual’s immune response, environmental factors, and different bacterial virulence factors of the individual bacterial strains. Eradication of the bacteria plays a crucial role in the treatment of these cases however antibiotic therapy does not always help. Bacteria often develop resistance to antibiotics so we recommend that not only screening for H. pylori also the strain determination should have some diagnostic value, especially in the patients who already developed gastritis. Furthermore, for such patients assessment of disease progression (atrophic or metaplastic gastritis) could be followed by polymorphism determination. Until now we cannot predict the disease based only on single polymorphism. Bacteria successfully neutralize the responses of the immune systems using different enzymes or even components of the host immune response. However, the influence of immune system and its components could represent new ways of treatments and could help to eradicate the infection.
Collapse
|
|
45
|
The influence of cytokine gene polymorphisms on the risk of developing gastric cancer in patients with Helicobacter pylori infection. Radiol Oncol 2015; 49:256-64. [PMID: 26401131 PMCID: PMC4577222 DOI: 10.2478/raon-2014-0041] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2014] [Accepted: 08/27/2014] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Helicobacter pylori infection is the main cause of gastric cancer. The disease progression is influenced by the host inflammatory responses, and cytokine single nucleotide polymorphisms (SNPs) may have a role in the course of the disease. The aim of our study was to investigate proinflammatory cytokine polymorphisms, previously associated with the development of gastric cancer, in a Slovenian population. PATIENTS AND METHODS In total 318 patients and controls were selected for the study and divided into three groups: (i) patients with gastric cancer (n = 58), (ii) patients with chronic gastritis (n = 60) and (iii) healthy control group (n = 200). H. pylori infection in patient groups was determined by serology, histology and culture. Four proinflammatory gene polymorphisms were determined (IL-1β, IL-1ra, TNF-α, TLR-4) in all subjects. RESULTS We found a statistically significant difference between males and females for the groups (p = 0.025). Odds ratio (OR) for gastric cancer risk for females was 0.557 (95% confidence interval [CI]: 0.233-1.329) and for chronic gastritis 2.073 (95% CI: 1.005-4.277). IL-1B-511*T/T homozygous allele for cancer group had OR = 2.349 (95% CI: 0.583-9.462), heterozygous IL-1B-511*T had OR = 1.470 (95% CI: 0.583-3.709) and heterozygotes in TNF-A-308 genotype for chronic gastritis had OR = 1.402 (95% CI: 0.626-3.139). Other alleles had OR less than 1. CONCLUSIONS We could not prove association between gastric cancer and chronic gastritis due to H. pylori in any cytokine SNPs studied in Slovenian population. Other SNPs might be responsible besides infection with H. pylori for the progression from atrophy to neoplastic transformation.
Collapse
|
|
46
|
Influence of functional polymorphisms in TNF-α, IL-8, and IL-10 cytokine genes on mRNA expression levels and risk of gastric cancer. Tumour Biol 2015; 36:9159-70. [PMID: 26088449 DOI: 10.1007/s13277-015-3593-x] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2014] [Accepted: 05/19/2015] [Indexed: 12/20/2022] Open
|
|
47
|
Hui M, Yan X, Jiang Y. The tumor necrosis factor-α-238 polymorphism and digestive system cancer risk: a meta-analysis. Clin Exp Med 2015; 16:367-74. [PMID: 26047868 DOI: 10.1007/s10238-015-0363-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2015] [Accepted: 05/26/2015] [Indexed: 12/12/2022]
Abstract
Many studies have reported the association between tumor necrosis factor-α (TNF-α)-238 polymorphism and digestive system cancer susceptibility, but the results were inconclusive. We performed a meta-analysis to derive a more precise estimation of the relationship between TNF-α-238 G/A polymorphism and digestive system cancer risk. Pooled analysis for the TNF-α-238 G/A polymorphism contained 26 studies with a total of 4849 cases and 8567 controls. The meta-analysis observed a significant association between TNF-α-238 G/A polymorphism and digestive system cancer risk in the overall population (GA vs GG: OR 1.19, 95 % CI 1.00-1.40, P heterpgeneity = 0.016; A vs G: OR 1.19, 95 % CI 1.03-1.39, P heterpgeneity = 0.015; dominant model: OR 1.20, 95 % CI 1.02-1.41, P heterpgeneity = 0.012). In the analysis of the ethnic subgroups, however, similar results were observed only in the Asian population, but not in the Caucasian population. Therefore, this meta-analysis suggests that TNF-α-238 G/A polymorphism is associated with a significantly increased risk of digestive system cancer. Further large and well-designed studies are needed to confirm these findings.
Collapse
Affiliation(s)
- Ming Hui
- Department of Gastroenterology, The Second Affiliated Hospital of Xinjiang Medical University, Urumchi, 830011, China
| | - Xiaojuan Yan
- Department of Emergency, Urumchi First People's Hospital, Urumchi, 830000, China
| | - Ying Jiang
- Department of Infectious Diseases, The Second Affiliated Hospital of Xinjiang Medical University, Urumchi, 830011, China. .,Department of Infectious Diseases, The Second Affiliated Hospital of Xinjiang Medical University, No. 38, Lane 2, Nanhu East Road, Urumchi, 830000, China.
| |
Collapse
|
|
48
|
The Prevalence of Helicobacter pylori Virulence Factors in Bhutan, Vietnam, and Myanmar Is Related to Gastric Cancer Incidence. BIOMED RESEARCH INTERNATIONAL 2015; 2015:830813. [PMID: 26090448 PMCID: PMC4450262 DOI: 10.1155/2015/830813] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/04/2014] [Revised: 01/26/2015] [Accepted: 01/31/2015] [Indexed: 12/24/2022]
Abstract
Gastric cancer is a significant health problem in Asia. Although the prevalence of Helicobacter pylori infection is similar in Bhutan, Vietnam, and Myanmar, the incidence of gastric cancer is highest in Bhutan, followed by Vietnam and Myanmar. We hypothesized that H. pylori virulence factors contribute to the differences. The status of cagA, vacA, jhp0562, and β-(1,3)galT(jhp0563) was examined in 371 H. pylori-infected patients from Bhutan, Vietnam, and Myanmar. Each virulence factor could not explain the difference of the incidence of gastric cancer. However, the prevalence of quadruple-positive for cagA, vacA s1, vacA m1, and jhp0562-positive/β-(1,3)galT-negative was significantly higher in Bhutan than in Vietnam and Myanmar and correlated with gastric cancer incidence. Moreover, gastritis-staging scores measured by histology of gastric mucosa were significantly higher in quadruple-positive strains. We suggest that the cagA, vacA s1, vacA m1, and jhp0562-positive/β-(1,3)galT-negative genotype may play a role in the development of gastric cancer.
Collapse
|
|
49
|
Rossi E, Basso D, Zambon CF, Navaglia F, Greco E, Pelloso M, Artuso S, Padoan A, Pescarin M, Aita A, Bozzato D, Moz S, Cananzi M, Guariso G, Plebani M. TNFA Haplotype Genetic Testing Improves HLA in Estimating the Risk of Celiac Disease in Children. PLoS One 2015; 10:e0123244. [PMID: 25915602 PMCID: PMC4411089 DOI: 10.1371/journal.pone.0123244] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2014] [Accepted: 02/28/2015] [Indexed: 12/13/2022] Open
Abstract
Background TNF-α and IFN-γ play a role in the development of mucosal damage in celiac disease (CD). Polymorphisms of TNFA and IFNG genes, as well as of the TNFRSF1A gene, encoding the TNF-α receptor 1, might underlie different inter-individual disease susceptibility over a common HLA risk background. The aims of this study were to ascertain whether five SNPs in the TNFA promoter (-1031T>C,-857C>T,-376G>A,-308G>A,-238G>A), sequence variants of the TNFRSF1A gene and IFNG +874A>T polymorphism are associated with CD in a HLA independent manner. Methods 511 children (244 CD, 267 controls) were genotyped for HLA, TNFA and INFG (Real Time PCR). TNFRSF1A variants were studied (DHPLC and sequence). Results Only the rare TNFA-1031C (OR=0.65, 95% CI:0.44-0.95), -857T (OR=0.42, 95% CI:0.27-0.65), -376A (OR=2.25, 95% CI:1.12-4.51) and -308A (OR=4.76, 95% CI:3.12-7.26) alleles were significantly associated with CD. One TNFRSF1A variant was identified (c.625+10A>G, rs1800693), but not associated with CD. The CD-correlated TNFA SNPs resulted in six haplotypes. Two haplotypes were control-associated (CCGG and TTGG) and three were CD-associated (CCAG, TCGA and CCGA). The seventeen inferred haplotype combinations were grouped (A to E) based on their frequencies among CD. Binary logistic regression analysis documented a strong association between CD and HLA (OR for intermediate risk haplotypes=178; 95% CI:24-1317; OR for high risk haplotypes=2752; 95% CI:287-26387), but also an HLA-independent correlation between CD and TNFA haplotype combination groups. The CD risk for patients carrying an intermediate risk HLA haplotype could be sub-stratified by TNFA haplotype combinations. Conclusion TNFA promoter haplotypes associate with CD independently from HLA. We suggest that their evaluation might enhance the accuracy in estimating the CD genetic risk.
Collapse
Affiliation(s)
- Elisa Rossi
- Department of Medicine—DIMED, University of Padova, Padova, Italy
| | - Daniela Basso
- Department of Laboratory Medicine, University—Hospital of Padova, Padova, Italy
- * E-mail:
| | | | - Filippo Navaglia
- Department of Laboratory Medicine, University—Hospital of Padova, Padova, Italy
| | - Eliana Greco
- Department of Medicine—DIMED, University of Padova, Padova, Italy
| | - Michela Pelloso
- Department of Medicine—DIMED, University of Padova, Padova, Italy
| | - Serena Artuso
- Unit of Pediatric Gastroenterology, Department of Women and Children's Health, University-Hospital of Padova, Padova, Italy
| | - Andrea Padoan
- Department of Medicine—DIMED, University of Padova, Padova, Italy
| | - Matilde Pescarin
- Unit of Pediatric Gastroenterology, Department of Women and Children's Health, University-Hospital of Padova, Padova, Italy
| | - Ada Aita
- Department of Medicine—DIMED, University of Padova, Padova, Italy
| | - Dania Bozzato
- Department of Medicine—DIMED, University of Padova, Padova, Italy
| | - Stefania Moz
- Department of Medicine—DIMED, University of Padova, Padova, Italy
| | - Mara Cananzi
- Unit of Pediatric Gastroenterology, Department of Women and Children's Health, University-Hospital of Padova, Padova, Italy
| | - Graziella Guariso
- Unit of Pediatric Gastroenterology, Department of Women and Children's Health, University-Hospital of Padova, Padova, Italy
| | - Mario Plebani
- Department of Medicine—DIMED, University of Padova, Padova, Italy
| |
Collapse
|
|
50
|
Polymorphisms of the IL-6, IL-8 and IL-10 genes and the risk of gastric pathology in patients infected with Helicobacter pylori. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2015; 50:153-159. [PMID: 25888319 DOI: 10.1016/j.jmii.2015.03.002] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/16/2014] [Revised: 02/04/2015] [Accepted: 03/05/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND/PURPOSE Helicobacter pylori-induced gastric mucosal inflammation is mediated by proinflammatory and anti-inflammatory cytokines. Polymorphisms in genes that code cytokines influence cytokine secretion levels and appear to contribute to the risk of gastric diseases. In this sense, we performed this study to identify the polymorphisms in the IL-6, IL-8, and IL-10 genes and their associations with H. pylori infection and gastric pathologies. METHODS Gastric biopsy samples of 151 patients infected with H. pylori and 76 uninfected individuals were used. Helicobacter pylori infection was diagnosed by histological examination and the detection of the ureA and glmM genes. The polymorphisms in the IL-6 (at position -174), IL-8 (at position -251), and IL-10 (at position -819) were detected by polymerase chain reaction-restriction fragment length polymorphism. RESULTS Among the genetic polymorphisms studied, we observed that only the presence of the A allele at position -251 of the IL-8 gene was significantly associated with H. pylori infection. In addition, patient carriers of the A/A genotype at position -251 of the IL-8 gene and carriers of the T allele at position -819 of the IL-10 gene had an increased risk of peptic ulcer disease in the presence of H. pylori infection. We did not find a correlation between polymorphisms in the IL-6, IL-8, and IL-10 genes and a higher risk of gastric carcinoma. CONCLUSION We demonstrated that polymorphisms in the IL-8 gene was significantly associated with H. pylori infection. Furthermore, polymorphisms in the IL-8 and IL-10 genes were associated with an enhanced risk of peptic ulcer disease in H. pylori-positive patients.
Collapse
|