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Chen YJ, Tai CS, Chang KC, Chen HL, Ni YH, Wu JF. Early predictors of intestinal complications in pediatric-onset Crohn's disease: A long-term cohort study in Taiwan. J Formos Med Assoc 2024:S0929-6646(24)00297-3. [PMID: 38937194 DOI: 10.1016/j.jfma.2024.06.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Revised: 06/18/2024] [Accepted: 06/20/2024] [Indexed: 06/29/2024] Open
Abstract
PURPOSE Identifying reliable prognostic factors for pediatric-onset Crohn's disease (CD) is important for guiding early treatment. This study aimed to evaluate the validity of various clinical parameters for predicting long-term intestinal complications in pediatric-onset CD patients with CD in Taiwan. METHODS This was a single-center, retrospective study. Patients diagnosed with CD under 18 years of age at our hospital between January 1999 and December 2021 were enrolled. The baseline clinical variables and the Pediatric Crohn's Disease Activity Index (PCDAI) were obtained. Patients were categorized into low-, medium-, or high-risk groups based on the 2020 European Crohn's and Colitis Organization and European Society for Pediatric Gastroenterology Hepatology and Nutrition (ECCO-ESPGHAN) guidelines. The primary endpoint was the occurrence of new intestinal complications. RESULTS Among 53 enrolled patients (33 males and 20 females), 8 patients (33.96%) developed intestinal complications during the follow-up period (median 6.42 years, 3.17-9.75 years). Patients in the initial ECCO-ESPGHAN medium- or high-risk group had a 4.71-fold higher risk of intestinal complications than those in the low-risk group [hazard ratio = 4.71, p = 0.023] after adjusting for PCDAI in the multivariate Cox proportional hazard analysis. The other clinical variables did not reach statistical significance in predicting intestinal complications. The positive and negative predictive values of the ECCO-ESPGHAN stratification method for intestinal complications were 48.15% and 80.77%, respectively. CONCLUSIONS ECCO-ESPGHAN risk stratification is an effective early predictor of long-term intestinal complications in the Taiwanese population and may be used in clinical practice to guide early advanced therapy.
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Affiliation(s)
- Yuh-Jue Chen
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan; Department of Pediatrics, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan
| | - Chi-Shan Tai
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
| | - Kai-Chi Chang
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
| | - Huey-Ling Chen
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan; College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Yen-Hsuan Ni
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan; College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Jia-Feng Wu
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan; College of Medicine, National Taiwan University, Taipei, Taiwan.
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Knisely MR, Conley YP, Szigethy E. Cytokine Genetic Variants and Health-Related Quality of Life in Crohn's Disease: An Exploratory Study. Biol Res Nurs 2019; 21:544-551. [PMID: 31272196 DOI: 10.1177/1099800419860906] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND Crohn's disease (CD) is an inflammatory condition that has deleterious effects on patients' health-related quality of life (HRQoL). Demographic, clinical, and psychosocial factors contribute to variability in HRQoL; however, the influence of genetic variations related to altered inflammatory responses in individuals with CD is unknown. This exploratory study compared HRQoL scores across genotypes of functional genetic polymorphisms in cytokine candidate genes among individuals with CD. METHOD This study used data and blood samples collected in a parent study in 39 patients with CD aged 15-30 years. Participant reports of HRQoL were collected using the Shortened Inflammatory Bowel Disease Questionnaire (SIBDQ). Genetic data were collected for 18 functional polymorphisms in eight cytokine candidate genes. SIBDQ scores were compared among genotypes using one-way, between-subjects analysis of variance. RESULTS SIBDQ scores differed across genotypes as follows: for IL-1R2 rs4141134 scores differed for total SIBDQ (p = .004) and systemic (p = .011), emotion (p = .038), and social domains (p = .025); for IL-10 rs1878672, scores differed for total SIBDQ (p = .031) and social domain (p = .008); for NFKB2 rs1056890, scores differed for social domain (p = .041); for TNF-α rs1800629, scores differed for total SIBDQ (p = .001) and bowel (p = .026), systemic (p = .014), and social domains (p = .045). CONCLUSIONS Findings on differences in SIBDQ scores across functional genetic polymorphisms in cytokine genes suggest potential mechanisms that contribute to variability in HRQoL in adolescents and young adults with CD.
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Affiliation(s)
| | - Yvette P Conley
- 2 School of Nursing, University of Pittsburgh, Pittsburgh, PA, USA.,3 Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA
| | - Eva Szigethy
- 4 Department of Gastroenterology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.,5 Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
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Rufini S, Ciccacci C, Novelli G, Borgiani P. Pharmacogenetics of inflammatory bowel disease: a focus on Crohn's disease. Pharmacogenomics 2017; 18:1095-1114. [PMID: 28686143 DOI: 10.2217/pgs-2017-0068] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Crohn's disease is an inflammatory bowel disease showing a high heterogeneity in phenotype and a strong genetic component. The treatment is complex, due to different severity of clinical parameters and to the fact that therapies only permit to control symptoms and to induce remission for short periods. Moreover, all categories of drugs present a great interindividual variability both in terms of efficacy and side effects appearance. For this reason, the identification of specific genomic biomarkers involved in drugs response will be of great clinical utility in order to foresee drug's efficacy and to prevent adverse reactions, permitting a more personalized therapeutic approach. In this review, we focus the attention on the pharmacogenetic studies regarding drugs commonly utilized in Crohn's disease treatment.
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Affiliation(s)
- Sara Rufini
- Department of Biomedicine & Prevention, Genetics Unit, University of Rome "Tor Vergata", Rome, Italy
| | - Cinzia Ciccacci
- Department of Biomedicine & Prevention, Genetics Unit, University of Rome "Tor Vergata", Rome, Italy
| | - Giuseppe Novelli
- Department of Biomedicine & Prevention, Genetics Unit, University of Rome "Tor Vergata", Rome, Italy
| | - Paola Borgiani
- Department of Biomedicine & Prevention, Genetics Unit, University of Rome "Tor Vergata", Rome, Italy
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Al-Meghaiseeb ES, Al-Robayan AA, Al-Otaibi MM, Arfin M, Al-Asmari AK. Association of tumor necrosis factor-α and -β gene polymorphisms in inflammatory bowel disease. J Inflamm Res 2016; 9:133-40. [PMID: 27382325 PMCID: PMC4918894 DOI: 10.2147/jir.s101225] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Inflammatory bowel disease (IBD) is a complex, multifactorial, chronic inflammatory disorder of the gastrointestinal tract in which immune dysregulation caused by genetic and/or environmental factors plays an important role. The aim of this case–control study was to evaluate the association of tumor necrosis factor-alpha (TNF-α) (308) and -β (+252) polymorphisms with susceptibility of IBD. A total of 379 Saudi subjects including 179 IBD patients (ulcerative colitis (UC) =84 and Crohn’s disease (CD) =95) and 200 age- and sex-matched healthy controls were recruited. TNF-α and TNF-β genes were amplified using an amplification refractory mutation systems polymerase chain reaction methodology to detect TNF-α (−308) and -β (+252) polymorphisms. The frequency of the GA genotype of TNF-α (−308G/A) was higher, and the frequencies of the GG and AA genotypes were significantly lower in IBD patients compared with those in controls, indicating that genotype GA-positive individuals are susceptible to IBD and that the GG and AA genotypes exert a protective effect. The frequency of allele A of TNF-α (−308G/A) was significantly higher and that of allele G was lower in IBD patients compared with those in controls, indicating an association of allele A with IBD risk in Saudi patients. On stratification of IBD patients into UC and CD, an almost similar pattern was noticed in both the groups. The results of TNF-β (+252A/G) polymorphisms showed a significant increase in the frequency of the GG genotype in IBD patients, suggesting a positive association of GG genotype with IBD risk. On stratification of IBD patients into UC and CD, the genotype GG of TNF-β was associated with susceptibility risk to UC but not CD. The frequencies of alleles and genotypes of both TNF-α and-β polymorphisms are not affected by sex or type of IBD (familial or sporadic). TNF-α (−308G/A) and TNF-β (+252A/G) polymorphisms are associated with risk of developing IBD in Saudi population.
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Affiliation(s)
| | | | | | - Misbahul Arfin
- Research Centre, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
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Association of inflammatory cytokine gene polymorphisms with inflammatory bowel disease in a Moroccan cohort. Genes Immun 2015; 17:60-5. [PMID: 26632999 DOI: 10.1038/gene.2015.52] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2015] [Revised: 10/13/2015] [Accepted: 10/21/2015] [Indexed: 02/08/2023]
Abstract
The purpose of this study was to investigate whether common variants in inflammatory and immune response genes influence inflammatory bowel disease (IBD) risk among Moroccan patients. Using a candidate gene approach, 10 single-nucleotide polymorphisms mapping on six genes (MIF_rs755622, TNFA_rs1800629, IL6_rs2069840, IL6R_rs2228145, IL6ST_rs2228044, IL17A (rs2275913, rs4711998, rs7747909, rs8193036, rs3819024)) were assessed in 510 subjects grouped in 199 IBD and 311 healthy controls. Genotyping was performed with the TaqMan allelic discrimination technology. The results were analyzed using PLINK software. The frequency of allele A for TNFA rs1800629 was significantly higher in ulcerative colitis (UC) patients compared with controls (30.16 vs 16.72%; P=0.0005; odds ratio (OR)=2.15; 95% confidence interval (CI)=1.39-3.32). Statistically significant association to UC was also found under dominant AA+AG vs GG (OR=1.85, 95% CI=1.07-3.21; P=0.02) and recessive models (OR=8.38; 95% CI=2.86-24.53; P=0.0001). In the same way, an association of TNFA rs1800629 variant was observed with IBD under recessive model AA vs AG+GG (OR=4.10; 95% CI=1.56-10.76; P=0.004). No evidence of significant associations was found for the remaining investigated polymorphisms. Our data suggest that TNFA gene promoter polymorphism participates in determining IBD susceptibility in Moroccan patients.
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Dosseva-Panova V, Mlachkova A, Popova C. Gene polymorphisms in periodontitis. Overview. BIOTECHNOL BIOTEC EQ 2015. [DOI: 10.1080/13102818.2015.1056230] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022] Open
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Sarlos P, Kovesdi E, Magyari L, Banfai Z, Szabo A, Javorhazy A, Melegh B. Genetic update on inflammatory factors in ulcerative colitis: Review of the current literature. World J Gastrointest Pathophysiol 2014; 5:304-21. [PMID: 25133031 PMCID: PMC4133528 DOI: 10.4291/wjgp.v5.i3.304] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2014] [Revised: 03/19/2014] [Accepted: 07/12/2014] [Indexed: 02/06/2023] Open
Abstract
Ulcerative colitis (UC) is one of the main types of inflammatory bowel disease, which is caused by dysregulated immune responses in genetically predisposed individuals. Several genetic factors, including interleukin and interleukin receptor gene polymorphisms and other inflammation-related genes play central role in mediating and modulating the inflammation in the human body, thereby these can be the main cause of development of the disease. It is clear these data are very important for understanding the base of the disease, especially in terms of clinical utility and validity, but summarized literature is exiguous for challenge health specialist that can used in the clinical practice nowadays. This review summarizes the current literature on inflammation-related genetic polymorphisms which are associated with UC. We performed an electronic search of Pubmed Database among publications of the last 10 years, using the following medical subject heading terms: UC, ulcerative colitis, inflammation, genes, polymorphisms, and susceptibility.
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Kwinta P, Pietrzyk JJ. Retinopathy of prematurity: is genetic predisposition an important risk factor? EXPERT REVIEW OF OPHTHALMOLOGY 2014. [DOI: 10.1586/17469899.2.2.275] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
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Bonyadi M, Abdolmohammadi R, Jahanafrooz Z, Somy MH, Khoshbaten M. TNF-alpha gene polymorphisms in Iranian Azari Turkish patients with inflammatory bowel diseases. Saudi J Gastroenterol 2014; 20:108-12. [PMID: 24705148 PMCID: PMC3987150 DOI: 10.4103/1319-3767.129475] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
CONTEXT Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases of the bowel (IBD) whose causes are not fully known. Emerging data indicate that alterations in cytokine synthesis may play a role in IBD pathogenesis. AIMS We aimed to determine the association between tumor necrosis factor-alfa (TNFα) promoter polymorphisms (at positions - 308 and - 1031) and susceptibility to IBD among Iranian Azari Turkish patients. SETTINGS AND DESIGN One hundred and one patients with IBD and 100 healthy subjects were analyzed. MATERIALS AND METHODS Both polymorphisms in the promoter region of the TNFα gene at positions -1031T/C and -308G/A were detected by polymerase chain reaction-restriction fragment length polymorphism assay. All statistical analyses were calculated with SPSS for Windows 16.0. The Fisher's exact test was used to test for departure from Hardy-Weinberg equilibrium of the genotype frequencies (P > 0.05). RESULTS The allele frequency of the TNFα-308G and -1031T were higher in IBD patients but did not reach statistical significance. However, the homozygous TT genotype for the SNP-1031 T > C was significantly higher in UC patients than in healthy controls (P = 0.01) and the heterozygous CT genotype for the SNP -1031 T > C was significantly lower in UC patients than in healthy controls (P = 0.03). CONCLUSIONS The TNFα-1031 T allele confers a significant risk for developing UC in Iranian Azeri Turkish patients. Also the frequency of TNFα-1031 C allele was considerably low among patients with UC and it may have protective role among them (OR = 0.43; P = 0.01).
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Affiliation(s)
- Mortaza Bonyadi
- Liver and Gastrointestinal Disease Research Centre of Tabriz University of Medical Sciences, Tabriz, Iran,Address for correspondence: Dr. Mortaza Bonyadi, Center of Excellence for Biodiversity, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran. E-mail:
| | - Reza Abdolmohammadi
- Liver and Gastrointestinal Disease Research Centre of Tabriz University of Medical Sciences, Tabriz, Iran
| | - Zohreh Jahanafrooz
- Department of Genetics, Center of Excellence for Biodiversity, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
| | - Mohammad-Hosein Somy
- Liver and Gastrointestinal Disease Research Centre of Tabriz University of Medical Sciences, Tabriz, Iran
| | - Manoochehr Khoshbaten
- Liver and Gastrointestinal Disease Research Centre of Tabriz University of Medical Sciences, Tabriz, Iran
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10
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Chronic Recurrent Multifocal Osteomyelitis. J Clin Immunol 2013; 33:1043-56. [DOI: 10.1007/s10875-013-9902-5] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2013] [Accepted: 04/29/2013] [Indexed: 01/26/2023]
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TNF-α Polymorphisms in Juvenile Idiopathic Arthritis: Which Potential Clinical Implications? Int J Rheumatol 2012; 2012:756291. [PMID: 23133455 PMCID: PMC3485518 DOI: 10.1155/2012/756291] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2012] [Revised: 07/13/2012] [Accepted: 08/03/2012] [Indexed: 02/06/2023] Open
Abstract
Whether tumor necrosis factor alpha (TNF-α) gene polymorphisms (SNPs) influence disease susceptibility and treatment of patients with juvenile idiopathic arthritis (JIA) is presently uncertain. TNF-α is one of the most important cytokine involved in JIA pathogenesis. Several single nucleotide polymorphisms (SNPs) have been identified within the region of the TNF-α gene but only a very small minority have proven functional consequences and have been associated with susceptibility to JIA. An association between some TNF-α SNPs and adult rheumatoid arthritis (RA) susceptibility, severity and clinical response to anti-TNF-α treatment has been reported. The most frenquetly studied TNF-α SNP is located at -308 position, where a substitution of the G allele with the rare A allele has been found. The presence of the allele -308A is associated to JIA and to a poor prognosis. Besides, the -308G genotype has been associated with a better response to anti-TNF-α therapy in JIA patients, confirming adult data. Psoriatic and oligoarticular arthritis are significantly associated to the -238 SNP only in some works. Studies considering other SNPs are conflicting and inconclusive. Large scale studies are required to define the contribution of TNF-α gene products to disease pathogenesis and anti-TNF-α therapeutic efficacy in JIA.
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Xie C, Liu XF, Yang MS. A meta-analysis on the association between three promoter variants of TNF-α and Crohn's disease. Mol Biol Rep 2012; 39:1575-1583. [PMID: 21633892 DOI: 10.1007/s11033-011-0896-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2011] [Accepted: 05/17/2011] [Indexed: 01/22/2023]
Abstract
Tumor necrosis factor-alpha (TNF-α) has been regarded as a candidate gene for Crohn's disease (CD) based on its inflammatory function in immune reaction and the clinical effectiveness of anti-TNF-α therapy. However, studies to date have reported inconsistent findings for the association between TNF-α and CD. The PubMed, EMBASE, and Medline databases were systematically reviewed from all English language publications up to April, 2011. A total of twenty-nine studies concerning the association between CD and the TNF-α promoter polymorphisms of -308G/A, -857C/T and -238G/A were identified, among of them only twenty-three studies match the inclusion criteria (including 3,843 cases and 6,260 controls) and were selected for the statistical test. We found that neither the G allele of -308G/A (OR 1.02, 95% CI 0.87-1.19, P = 0.84), C allele of -857C/T (OR 0.97, 95% CI 0.86-1.09, P = 0.57) and G allele of -238G/A (OR 0.91, 95% CI 0.70-1.18, P = 0.48), and nor their GG (OR 1.05, 95% CI 0.88-1.25, P = 0.59), CC (OR 0.98, 95% CI 0.86-1.12, P = 0.76) and GG (OR 0.92, 95% CI 0.70-1.21, P = 0.55) genotypes were associated with CD susceptibility, respectively. Our meta-analysis demonstrates that three promoter polymorphisms of TNF-α above may not confer susceptibility to CD.
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Affiliation(s)
- Cui Xie
- Laboratory of Disorder Genes and Department of Pharmacology, College of Pharmacy, Chongqing Medical University, 1 Yi Xue Yuan Road, P. O. Box 380, Chongqing 400016, People's Republic of China
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Association of TNF-alpha genetic polymorphisms with hepatocellular carcinoma susceptibility: a case-control study in a Han Chinese population. Int J Biol Markers 2011; 26:181-7. [PMID: 21928250 DOI: 10.5301/jbm.2011.8580] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/04/2011] [Indexed: 12/16/2022]
Abstract
The single nucleotide polymorphisms (SNPs) within the tumor necrosis factor-a (TNF-a) gene promoter region have been reported to be associated with susceptibility to various types of cancers. A case-control study (126 hepatocellular carcinoma [HCC] patients and 126 normal controls) was conducted to elucidate their possible association with the risk of hepatitis B virus (HBV)-related HCC in a Han Chinese population. TNF-alpha polymorphisms -1031T/C, -863C/A, -857C/T, -308G/A, and -238G/A were genotyped by polymerase chain reaction (PCR) and direct DNA sequencing. Disease associations were analyzed by the chi-square test or Fisher's exact test. When analyzed by overall groups, no significant differences in genotype and allele distributions were observed between the control and cases. However, stratified analysis according to sex showed that the frequency of the homozygous C allele of the -857 polymorphism was lower in female cases than in female controls (62.9% vs. 88.9%, p=0.026). In addition, further haplotype analysis revealed that the TCCGA (-1031/-863/-857/-308/-238) was more frequent in controls than cases (p=0.018; odds ratio = 0.266; 95% confidence interval, 0.083-0.857). These results indicated that the TNF-alpha-857C/T polymorphism may modify HBV-related HCC risk among women, and the haplotype TCCGA (-1031/-863/-857/-308/-238) may account for a decreased susceptibility to HCC development in the Han Chinese population. Additional studies in patients with different ethnic backgrounds are needed to validate these finding and to further explore the genetic pathogenesis of HBV-related HCC.
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Relationship between the polymorphism of tumor necrosis factor-α-308 G>A and susceptibility to inflammatory bowel diseases and colorectal cancer: a meta-analysis. Eur J Hum Genet 2011; 19:432-7. [PMID: 21248737 DOI: 10.1038/ejhg.2010.159] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023] Open
Abstract
Inflammatory bowel disease (IBD) and colorectal cancer (CRC) are common health problems worldwide. Tumor necrosis factor (TNF) is a type of cytokine that induces inflammation and inhibits tumorigenesis. Several studies have assessed the relationship between the polymorphism of TNF-α-308 G>A and the susceptibility to IBD and CRC; however, the results have been controversial. In addition, the hypothesis whether the increased risk of CRC in IBD patients could be partly ascribed to the polymorphism of TNF-α-308 G>A was unclear. Therefore, we conducted this meta-analysis to confirm these associations. Pooled odd ratios (ORs) and 95% confidence intervals (95% CIs) were calculated on the basis of data from 14, 18, and 7 studies from a total of 27 studies for the associations between the polymorphism of TNF-α-308 G>A and ulcerative colitis, Crohn's disease (CD) and CRC. In Europeans, the AA genotype increased the risk of ulcerative colitis (UC) (OR, 2.041; 95% CI, 1.261-3.301) and CD (OR, 1.730; 95% CI, 1.168-2.564) significantly, without obvious heterogeneity and publication bias. Meanwhile, the GA genotype increased the risk of UC in Asians (OR, 2.360; 95% CI, 1.269-4.390) significantly. However, no significant association was observed for CRC in any ethnic population. The results of this meta-analysis suggested that the polymorphism of TNF-α-308 G>A participates in modifying the susceptibility to UC and CD in Europeans and Asians. The increased risk of CRC in IBD patients should be clarified as the combined effects of polymorphisms in TNF-α and other cytokines, and the interaction with environmental factors, in future studies.
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Kuwahara A, Yamamori M, Fujita M, Okuno T, Tamura T, Kadoyama K, Okamura N, Nakamura T, Sakaeda T. TNFRSF1B A1466G genotype is predictive of clinical efficacy after treatment with a definitive 5-fluorouracil/cisplatin-based chemoradiotherapy in Japanese patients with esophageal squamous cell carcinoma. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH : CR 2010; 29:100. [PMID: 20646319 PMCID: PMC2915971 DOI: 10.1186/1756-9966-29-100] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/14/2010] [Accepted: 07/20/2010] [Indexed: 11/10/2022]
Abstract
BACKGROUND Currently definitive 5-fluorouracil (5-FU)/cisplatin (CDDP) -based chemotherapy is recognized as one of the most promising treatments for esophageal cancer. A series of studies performed found genetic polymorphisms and the plasma concentration of 5-FU to be predictive of acute severe toxicities and clinical response. Genetic polymorphisms of tumor necrosis factor (TNF) -alpha and its surface receptors, TNFRSF1A and TNFRSF1B have been examined in terms of susceptibility to various cancers. In this study, genetic polymorphisms of TNFRSF1B gene were evaluated Japanese esophageal squamous cell carcinoma (ESCC) patients treated with the definitive 5-FU/CDDP-based chemoradiotherapy and their predictive values of prognosis or severe acute toxicities were assessed. METHODS Forty-six patients with ESCC were treated with the definitive 5-FU/CDDP-based chemoradiotherapy, one course of which consisted of the continuous infusion of 5-FU for days 1-5 and 8-12, the infusion of CDDP on days 1 and 8, and the radiation at 2 Gy/day on days 1-5, 8-12, and 15-19, with a second course repeated after 2-week interval. Genetic polymorphisms of a TNF-alpha receptor TNFRSF1B gene were determined by a TaqMan(R) MGB probe-based polymerase chain reaction. RESULTS The genotype of TNFSR1B A1466G, but not M196R/T587G or C1493T, was found to be predictive of clinical response, i.e., a complete response or not (p = 0.040). Clinical response was predicted by tumor size (p = 0,002), lymph node metastasis (p = 0.007), distant metastasis (p = 0.001) and disease stage (p < 0.001), but TNFRSF1B A1466G genotype was independent of these factors. CONCLUSIONS Genetic polymorphism of TNFRSF1B A1466G was found to be predictive response in Japanese ESCC patients with a definitive 5-FU/CDDP-based chemoradiotherapy. Further clinical investigation with a large number of patients or experiments in vitro should be performed to assess the predictive value of TNFRSF1B A1466G genotype after chemoradiotherapy.
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Affiliation(s)
- Akiko Kuwahara
- School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya 663-8179, Japan
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Bernstein JM, Anon JB, Rontal M, Conroy J, Wang C, Sucheston L. Genetic polymorphisms in chronic hyperplastic sinusitis with nasal polyposis. Laryngoscope 2009; 119:1258-64. [PMID: 19405090 DOI: 10.1002/lary.20239] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
OBJECTIVES/HYPOTHESIS Although many proinflammatory cytokines have been identified in nasal polyp tissue, the initial trigger that causes this inflammation characterized by edema, lymphocytosis, and eosinophilia, is still unknown. The purpose of the present study is to identify the presence of genetic polymorphisms in proinflammatory, anti-inflammatory, and chemokine genes that might contribute to genetic susceptibility to chronic hyperplastic sinusitis with nasal polyposis (CHSwNP). STUDY DESIGN Case control study. METHODS Buccal swabs were taken from the left and right oral mucosal surfaces from 179 patients with CHSwNP and 153 nonpolyposis controls with the Purgene DNA purification protocol (Gentra). Genotyping assays for cytokine gene loci were performed on 14 cytokine genes using the iPlex Gold and the Mass Array Compact system (Sequenom, San Diego, CA). Tests of Hardy-Weinberg equilibrium proportions were performed separately in the cases and controls. Tests for evidence of association between alleles at each single-nucleotide polymorphism (SNP) and case-control status were performed using unconditional logistic regression. RESULTS The frequency of the A allele in a SNP located in tumor necrosis factor (TNF)-alpha (rs1800629) is significantly different in patients with nasal polyposis versus controls without nasal polyposis, 18.6% and 11.5%, respectively with an individuals' odds of susceptibility to nasal polyps increasing almost two-fold (odds ratio, 1.86; confidence interval, 1.4-3.09) given at least one copy of the A allele at this SNP. All other cytokine gene polymorphisms of both inflammatory, anti-inflammatory, and chemokine genes were not statistically different between the two groups. CONCLUSIONS TNF-alpha-308, a SNP in the promoter region of this cytokine gene is associated with increased odds of developing nasal polyposis. TNF-alpha is a potent immuno-mediator and proinflammatory cytokine that has been implicated in the pathogenesis of a large number of human diseases. The location of this gene on the short arm of chromosome 6, with the major histocompatibility complex genes and complement, has raised the probability that polymorphism within this locus may contribute to a genetic association of this region of the genome with a wide variety of infectious and autoimmune diseases.
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Affiliation(s)
- Joel M Bernstein
- Department of Otolaryngology, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, New York, USA.
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Bossa F, Colombo E, Andriulli A, Annese V. Treatment of steroid-naive ulcerative colitis. Expert Opin Pharmacother 2009; 10:1449-1460. [PMID: 19445560 DOI: 10.1517/14656560902973728] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
The introduction of steroid therapy by Truelove and Witts in the 1950s revolutionized the treatment of ulcerative colitis. Corticosteroids are potent inhibitors of T-cell activation and proinflammatory cytokines and still represent the mainstay of therapy of patients with ulcerative colitis. About 15% of patients are resistant to steroids, and about a quarter of patients become dependent within 1 year of therapy. Steroid-related adverse events are numerous and occur frequently. So, new steroids with low systemic absorption and better safety profile have been studied, but they show an overall lower efficacy compared with traditional steroids. A new drug-delivery system based on the use of autologous erythrocytes loaded with dexamethasone 21-phosphate has been recently developed. Several studies have demonstrated its efficacy in steroid-dependent patients leading to complete withdrawal of oral steroids and disappearance of the most steroid-related adverse events. In this review we elaborate on the role of steroids in the treatment of ulcerative colitis, focusing on the aspects related to the mechanisms of action and resistance to the steroids, and their secondary effects. Moreover, we analyse the alternatives to traditional systemic steroids such as the new steroids with low bioavailability and the steroids encapsulated into erythrocytes.
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Affiliation(s)
- Fabrizio Bossa
- Casa Sollievo della Sofferenza Hospital - IRCCS, Unit of Gastroenterology and Digestive Endoscopy, Viale Cappuccini 1, 71013 San Giovanni Rotondo (FG), Italy.
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18
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Harris L, Senagore P, Young VB, McCabe LR. Inflammatory bowel disease causes reversible suppression of osteoblast and chondrocyte function in mice. Am J Physiol Gastrointest Liver Physiol 2009; 296:G1020-9. [PMID: 19299577 PMCID: PMC4059386 DOI: 10.1152/ajpgi.90696.2008] [Citation(s) in RCA: 54] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Decreased bone density and stature can occur in pediatric patients with inflammatory bowel disease (IBD). Little is known about how IBD broadly impacts the skeleton. To evaluate the influence of an acute episode of IBD on growing bone, 4-wk-old mice were administered 5% dextran sodium sulfate (DSS) for 5 days to induce colitis and their recovery was monitored. During active disease and early recovery, trabecular bone mineral density, bone volume, and thickness were decreased. Cortical bone thickness, outer perimeter, and density were also decreased, whereas inner perimeter and marrow area were increased. These changes appear to maintain bone strength since measures of moments of inertia were similar between DSS-treated and control mice. Histological (static and dynamic), serum, and RNA analyses indicate that a decrease in osteoblast maturation and function account for changes in bone density. Unlike some conditions of bone loss, marrow adiposity did not increase. Similar to reports in humans, bone length decreased and correlated with decreases in growth plate thickness and chondrocyte marker expression. During disease recovery, mice experienced a growth spurt that led to their achieving final body weights and bone length, density, and gene expression similar to healthy controls. Increased TNF-alpha and decreased IGF-I serum levels were observed with active disease and returned to normal with recovery. Changes in serum TNF-alpha (increased) and IGF-I (decreased) paralleled changes in bone parameters and returned to normal values with recovery, suggesting a potential role in the skeletal response.
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Cheung YF, Huang GY, Chen SB, Liu XQ, Xi L, Liang XC, Huang MR, Chen S, Huang LS, Liu XQ, Chan KW, Lau YL. Inflammatory gene polymorphisms and susceptibility to kawasaki disease and its arterial sequelae. Pediatrics 2008; 122:e608-14. [PMID: 18710885 DOI: 10.1542/peds.2008-0646] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
OBJECTIVE We tested the hypothesis that single-nucleotide polymorphisms of inflammatory genes C-reactive protein (CRP) and tumor necrosis factor alpha (TNF-alpha) may exert influence on susceptibility to Kawasaki disease and its arterial sequelae. METHODS We analyzed the CRP +1444 C-->T and TNF-alpha -308 G-->A polymorphisms in 167 patients aged 8.9 +/- 4.1 years with a history of Kawasaki disease (73 with and 94 without coronary aneurysms) and 124 healthy control subjects. For patients with Kawasaki disease, we further determined whether these single-nucleotide polymorphisms were associated with coronary aneurysms, carotid arterial stiffening, and intima-media thickness. RESULTS Genotypic and allelic frequencies of CRP +1444 for T carrier and TNF-alpha -308 for A carrier were significantly higher in patients than in control subjects. The genotypic and allelic distributions did not differ between patients with and those without coronary aneurysms; however, patients with CRP +1444 CT/TT genotype compared with those with a CC genotype and patients with TNF-alpha -308 GA/AA genotype compared with those with a GG genotype had significantly greater carotid arterial stiffness and intima-media thickness. Carriers of both CRP +1444 T allele and TNF-alpha -308 A allele had the highest susceptibility to Kawasaki disease and a significant trend of increased arterial stiffness and intima-media thickness compared with those who carried either 1 or none of the rare alleles. Multiple linear regression analysis identified CRP +1444 allele carrier as a significant determinant of both carotid stiffness and carotid intima-media thickness and TNF-alpha -308 A allele carrier as a determinant of only intima-media thickness. CONCLUSIONS Our findings suggest that CRP +1444 C-->T and TNF-alpha -308 G-->A polymorphisms are associated with predisposition to Kawasaki disease and, in patients with Kawasaki disease, increased carotid arterial stiffness and intima-media thickness in the long-term.
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Affiliation(s)
- Yiu-Fai Cheung
- Grantham Hospital, University of Hong Kong, Division of Pediatric Cardiology, Department of Pediatrics and Adolescent Medicine, 125 Wong Chuk Hang Rd, Hong Kong, China.
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20
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Ferguson LR, Huebner C, Petermann I, Gearry RB, Barclay ML, Demmers P, McCulloch A, Han DY. Single nucleotide polymorphism in the tumor necrosis factor-alpha gene affects inflammatory bowel diseases risk. World J Gastroenterol 2008; 14:4652-61. [PMID: 18698679 PMCID: PMC2738789 DOI: 10.3748/wjg.14.4652] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
AIM: To investigate the role that single nucleotide polymorphisms (SNPs) in the promoter of the tumour necrosis factor-alpha (TNF-α) gene play in the risk of inflammatory bowel diseases (IBDs) in a New Zealand population, in the context of international studies.
METHODS: DNA samples from 388 patients with Crohn’s disease (CD), 405 ulcerative colitis (UC), 27 indeterminate colitis (IC) and 201 randomly selected controls, from Canterbury, New Zealand were screened for 3 common polymorphisms in the TNF-α receptor: -238 G→A, -308 G→A and -857C→T, using a TaqmanR assay. A meta-analysis was performed on the data obtained on these polymorphisms combined with that from other published studies.
RESULTS: Individuals carrying the -308 G/A allele had a significantly (OR = 1.91, χ2 = 17.36, P < 0.0001) increased risk of pancolitis, and a 1.57-fold increased risk (OR = 1.57, χ2 = 4.34, P = 0.037) of requiring a bowel resection in UC. Carrying the -857 C/T variant decreased the risk of ileocolonic CD (OR = 0.56, χ2 = 4.32, P = 0.037), and the need for a bowel resection (OR = 0.59, χ2 = 4.85, P = 0.028). The risk of UC was reduced in individuals who were smokers at diagnosis, (OR = 0.48, χ2 = 4.86, P = 0.028).
CONCLUSION: TNF-α is a key cytokine known to play a role in inflammatory response, and the locus for the gene is found in the IBD3 region on chromosome 6p21, known to be associated with an increased risk for IBD. The -308 G/A SNP in the TNF-α promoter is functional, and may account in part for the increased UC risk associated with the IBD3 genomic region. The -857 C/T SNP may decrease IBD risk in certain groups. Pharmaco- or nutrigenomic approaches may be desirable for individuals with such affected genotypes.
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21
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Hradsky O, Lenicek M, Dusatkova P, Bronsky J, Nevoral J, Valtrova V, Kotalova R, Szitanyi P, Petro R, Starzykova V, Bortlik M, Vitek L, Lukas M, Cinek O. Variants of CARD15, TNFA and PTPN22 and susceptibility to Crohn's disease in the Czech population: high frequency of the CARD15 1007fs. ACTA ACUST UNITED AC 2008; 71:538-47. [PMID: 18489434 DOI: 10.1111/j.1399-0039.2008.01047.x] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Crohn's disease (CD) has been shown to be associated with the variants in the CARD15 gene as well as in other genes involved in the immune response. The frequencies of the variants profoundly differ among populations and so does the associated risk. We examined the associations of variants in the CARD15, TNFA and PTPN22 genes with pediatric-onset and adult-onset CD in the Czech population. Genotype, phenotype and allelic frequencies were compared between 345 patients with CD (136 pediatric-onset and 209 adult-onset patients) and 501 unrelated healthy controls. At least one minor allele of the CARD15 gene was carried by 46% patients and only 21% control subjects (OR = 3.2, 95% CI 2.4-4.4). In a multiple logistic regression model, the strongest association with CD was found for the 1007fs variant (OR = 4.6, 95% CI 3.0-7.0), followed by p.G908R (OR = 2.9, 95% CI 1.5-5.7) and p.R702W (OR = 1.7, 95% CI 1.0-2.9), while no independent association was found for the remaining variants in the CARD15 gene (p.268S, p.955I and p.289S), for the p.R620W variant in the PTPN22 gene or for the g.-308G>A variant in the TNFA gene. The age at CD onset was strongly modified by positivity for the 1007fs allele: it was present in 42% pediatric-onset and only 25% adult-onset patients. In conclusion, we report a high frequency of the minor allele of the CARD15 1007fs polymorphism in the Czech population and a strong effect of this allele on the age at disease onset.
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Affiliation(s)
- O Hradsky
- Department of Pediatrics, University Hospital Motol, Prague, Czech Republic
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Xiao YL, Miao YL. Research progress in susceptibility genes of inflammatory bowel disease. Shijie Huaren Xiaohua Zazhi 2008; 16:2259-2266. [DOI: 10.11569/wcjd.v16.i20.2259] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a group of non-specific chronic inflammatory conditions of the gastrointestinal tract with unknown complex etiology. Epidemiologic data indicate genetic contribution to IBD pathogenesis, which include familial aggregation, twin studies, racial and ethnic differences in disease prevalence. The most widely adopted approaches to identifying susceptibility genes in IBD include linkage studies, genome-wide association (GWA) studies and microarray. The first two technologies have confirmed NOD2, IL23R and other genes implicated in IBD pathogenesis and advances in microarray technology makes it possible to diagnose IBD at gene expression level. This article reviewed IBD related genes and introduced application of microarray to IBD research.
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Montecucco F, Mach F. New evidences for C-reactive protein (CRP) deposits in the arterial intima as a cardiovascular risk factor. Clin Interv Aging 2008; 3:341-349. [PMID: 18686755 PMCID: PMC2546477 DOI: 10.2147/cia.s2706] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Inflammatory processes are orchestrated by several soluble molecules, which interact with cell populations involved. Cytokines, chemokines, acute-phase reactants, and hormones are crucial in the evolution of several inflammatory disorders, such as atherosclerosis. Several evidences suggest that C-reactive protein (CRP) started to be considered as a cardiovascular risk factor, since CRP directly induces atheroslerosis development. The recent demonstration of CRP production not only by the liver, but also within atherosclerotic plaques by activated vascular cells, also suggests a possible dual role, as both a systemic and tissue agent. Although more studies are needed, some therapeutic approaches to reduce CRP levels have been performed with encouraging results. However, given the strong limitations represented by its low specificity and still accordingly with the American Heart Association, there is no need for high sensitivity CRP screening of the entire adult population as a public-health measure. The measure of serum CRP might be useful only for patients who are considered at intermediate risk.
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Affiliation(s)
- Fabrizio Montecucco
- Division of Cardiology, Foundation for Medical Research, University Hospital, Geneva, Switzerland
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Girschick HJ, Zimmer C, Klaus G, Darge K, Dick A, Morbach H. Chronic recurrent multifocal osteomyelitis: what is it and how should it be treated? ACTA ACUST UNITED AC 2007; 3:733-8. [PMID: 18037933 DOI: 10.1038/ncprheum0653] [Citation(s) in RCA: 88] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2007] [Accepted: 08/23/2007] [Indexed: 11/09/2022]
Abstract
BACKGROUND Chronic recurrent multifocal osteomyelitis (CRMO) is the most severe form of chronic nonbacterial osteomyelitis. In children and adolescents, chronic nonbacterial osteomyelitis predominantly affects the metaphyses of the long bones, but lesions can occur at any site in the skeleton. Other organs (the skin, eyes, gastrointestinal tract and lungs) can also be affected. Clinical diagnosis is often difficult because the symptoms and course of disease vary significantly. We present a 10-year-old girl diagnosed with CRMO involving several vertebrae, the femur and the metatarsus. INVESTIGATIONS Physical examination, abdominal ultra sonography, conventional X-ray, MRI, technetium bone scan, esophagogastroduodenoscopy, colonoscopy, tests for HLA-B27 and thiopurine methyltransferase, polymerase chain reaction and thoracic vertebral bone biopsies. DIAGNOSIS CRMO and Crohn's disease. MANAGEMENT The patient's condition improved whilst being treated with NSAIDs for 3 months; however, the patient had an allergic skin reaction to this therapy. Treatment was switched to sulfasalazine, accompanied by 3 weeks of therapy using oral prednisone, but sulfasalazine was discontinued 2 months later because the patient exhibited a minor elevation in the levels of liver enzymes. The patient was free of musculoskeletal symptoms for 6 months, at which time she started to complain again about pain in her back and bowel. Multimodal therapy, consisting of mesasalazine, corticosteroids (budesonide) and azathioprine, induced clinical remission of Crohn's disease.
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Affiliation(s)
- Hermann J Girschick
- Children's Hospital, University of Wuerzburg, Josef-Schneider-Strasse 2, Wuerzburg, 97080, Germany.
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Scapoli C, Mamolini E, Trombelli L. Role of IL-6, TNF-A and LT-A variants in the modulation of the clinical expression of plaque-induced gingivitis. J Clin Periodontol 2007; 34:1031-8. [DOI: 10.1111/j.1600-051x.2007.01145.x] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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Association of MIF-173 gene polymorphism with inflammatory bowel disease in Chinese Han population. Cytokine 2007; 41:44-7. [PMID: 18054247 DOI: 10.1016/j.cyto.2007.10.010] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2007] [Revised: 08/05/2007] [Accepted: 10/17/2007] [Indexed: 12/14/2022]
Abstract
AIM To study whether macrophage migration inhibitory factor (MIF)-173 gene polymorphism correlates with inflammatory bowel disease (IBD) in Chinese Han population. METHODS MIF-173 single nucleotide polymorphism (SNP) was genotyped by tetra-primer amplification refractory mutation system (ARMS) and restriction fragment length polymorphisms (RFLP)-PCR in 142 healthy subjects and 98 patients with inflammatory bowel disease (IBD). RESULTS There were no discrepancies between the results obtained by tetra-primer ARMS and RFLP-PCR. The frequency of MIF-173 CC genotype was significantly higher in patients with ulcerative colitis (UC) 15.5% than in healthy individuals 5.6% (chi(2)=6.066, P=0.018, OR=3.067 and 95% CI=1.257-7.482). There was a trend towards a higher frequency of CC genotype among CD patients compared with healthy controls, however this did not attain the statistical significance (P=0.245). CONCLUSION MIF-173 CC genotype may be associated with susceptibility to UC.
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27
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Vishnoi M, Choudhuri G, Mittal B. Is IL-10-819C/T gene polymorphism modulating the risk of gallbladder disease in north Indian population? J Gastrointest Cancer 2007; 38:46-51. [PMID: 19065724 DOI: 10.1007/s12029-008-9016-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
BACKGROUND Gallbladder carcinoma (GBC) is a highly aggressive neoplasm that arises in the background of gall stones and inflammation. Anti-inflammatory cytokine interleukin-10 (IL-10) gene polymorphisms have been associated with susceptibility to various inflammatory diseases and cancers. AIM of the study The aim of the present study was to investigate whether IL-10-819C/T polymorphism is associated with GBC susceptibility. METHODS The study subjects comprised 124 GBC patients, 135 patients with symptomatic gallstone disease, and 200 healthy subjects. Genomic DNA was extracted from blood leukocytes and IL-10-819C/T gene polymorphism was analyzed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS Frequency distributions of IL-10-819C/T genotypes were similar in GBC, gallstone patients, and healthy subjects. However, after stratification on the basis of sex, in male GBC patients, the TT genotype of IL-10-819C/T polymorphism showed an approximately sevenfold risk (p value = 0.038; odds ratio = 6.58; 95% confidence interval = 1.11-39.11) in the presence of gall stones when compared with gallstone patients. CONCLUSION These results suggest that interplay of sex hormones and IL-10-819C/T polymorphism may lead to the susceptibility of gallstone-mediated gallbladder carcinogenesis.
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Affiliation(s)
- Monika Vishnoi
- Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow 226014, India
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Goyette P, Labbé C, Trinh TT, Xavier RJ, Rioux JD. Molecular pathogenesis of inflammatory bowel disease: genotypes, phenotypes and personalized medicine. Ann Med 2007; 39:177-99. [PMID: 17457716 DOI: 10.1080/07853890701197615] [Citation(s) in RCA: 93] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Crohn's disease (CD) and ulcerative colitis (UC), also known as inflammatory bowel diseases (IBD), are characterized by chronic inflammation of the gastrointestinal tract. IBD is among the few complex diseases for which several genomic regions and specific genes have been identified and confirmed in multiple replication studies. We will review the different loci implicated in disease risk in the context of three proposed mechanisms leading to chronic inflammation of the gut mucosa: 1) deregulation of the innate immune response to enteric microflora or pathogens; 2) increased permeability across the epithelial barrier; and 3) defective regulation of the adaptive immune system. As our knowledge of genetic variation, analytical approaches and technology improves, additional genetic risk factors are expected to be identified. With the identification of novel risk variants, additional pathophysiological mechanisms are likely to emerge. The resulting discoveries will further our molecular understanding of IBD, potentially leading to improved disease classification and rational drug design. Moreover, these approaches and tools can be applied in the context of variable drug response with the goal of providing more personalized clinical management of patients with IBD.
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Affiliation(s)
- Philippe Goyette
- Université de Montréal, Department of Medicine, Montréal, Québec, Canada
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