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Yang QH, Zhang CN. Comparative study on the pathogenesis of Crohn’s disease and ulcerative colitis. World J Gastroenterol 2025; 31:106406. [DOI: 10.3748/wjg.v31.i19.106406] [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] [Received: 02/25/2025] [Revised: 03/25/2025] [Accepted: 04/25/2025] [Indexed: 05/21/2025] Open
Abstract
Inflammatory bowel disease (IBD) is an incurable disease of the digestive system; however, the therapeutic methods for IBD remain limited. The pathogenesis of IBD was systematically discussed and compared in this paper, primarily comprising Crohn’s disease and ulcerative colitis. This paper focused on six common aspects: (1) Dysregulated immune responses; (2) Gene function changes; (3) Intestinal microbes disorder and imbalance; (4) Microbial infections; (5) Associations between IBD and other inflammatory diseases; and (6) Other factors. In addition, the pathogenesis differences between these two forms of IBD were unraveled and clearly distinguished. These unique aspects of pathogenesis provide crucial insights for the precise treatment of both Crohn’s disease and ulcerative colitis. This paper illustrates the root causes and beneficial factors of resistance to IBD, which provides novel insights on early prevention, development of new therapeutic agents, and treatment options of this disease.
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Affiliation(s)
- Qi-Hang Yang
- Chinese Academy of Medical Science & Peking Union Medical College, Institute of Biomedical Engineering, Tianjin 300192, China
- University College London, Cancer Institute, London WC1E 6BT, United Kingdom
| | - Chuang-Nian Zhang
- Chinese Academy of Medical Science & Peking Union Medical College, State Key Laboratory of Advanced Medical Materials and Devices, Engineering Research Center of Pulmonary and Critical Care Medicine Technology and Device (Ministry of Education), Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Tianjin Institutes of Health Science, Tianjin 300192, China
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Zhou RN, Ruan GC, Wu MX, Guo MY, Liang HZ, Bai XY, Yang H. Interaction of Th17 differentiations-related gene polymorphisms and environmental factors contributing to the disease classification, complications, and surgical risks of Crohn's disease in the Chinese Han population. J Dig Dis 2024; 25:368-379. [PMID: 39075019 DOI: 10.1111/1751-2980.13301] [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: 09/26/2023] [Revised: 05/15/2024] [Accepted: 06/20/2024] [Indexed: 07/31/2024]
Abstract
OBJECTIVES Few studies have been conducted on gene-environment interactions in the Chinese population with Crohn's disease (CD). We aimed to investigate the association between single nucleotide polymorphisms (SNPs) on the T helper 17 (Th17) cell and CD susceptibility/performance in Chinese individuals. METHODS We conducted a case-control and case-only study at the Peking Union Medical College Hospital. Four SNPs related to the Th17 cell pathway genes were prioritized, including rs2284553 (interferon gamma receptor 2), rs7517847 (interleukin 23 receptor), rs7773324 (interferon regulatory factor 4), and rs4263839 (tumor necrosis factor superfamily 15). SNP frequency was calculated, and gene-environment interaction was assessed by multifactor dimensionality reduction analysis. RESULTS Altogether 159 CD patients and 316 healthy controls were included. All analyzed SNPs were found in Hardy-Weinberg equilibrium (P > 0.05). The frequency of rs2284553-A allele and rs4263839-A allele were lower in CD patients compared with controls (P < 0.05). While the rs4263839-A allele was more prevalent in ileocolonic CD patients than in those with isolated small intestinal or colonic disease (P = 0.035). Gene-environment interactions revealed associations between rs2284553 and breastfeeding, sunshine exposure, and fridge-stored food, affecting age at diagnosis, intestinal involvement, and intestinal stricture. Interaction of rs4263839 and breastfeeding influenced small intestinal lesions and intestinal stricture in CD. CONCLUSIONS This study provided information on the genetic background in Chinese CD patients. Incorporating these SNPs into predictive models may improve risk assessment and outcome prediction. Gene-environment interaction contributes to the understanding of CD pathogenesis.
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Affiliation(s)
- Ru Ning Zhou
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ge Chong Ruan
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy Medical Sciences and Peking Union Medical College, Beijing, China
| | - Mei Xu Wu
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ming Yue Guo
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hao Zheng Liang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiao Yin Bai
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hong Yang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy Medical Sciences and Peking Union Medical College, Beijing, China
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Akadam-Teker AB, Akşan B. Association of IL-17F rs763780 polymorphism and risk of psoriasis in Turkish population: a case-control study. An Bras Dermatol 2024; 99:357-361. [PMID: 38331704 DOI: 10.1016/j.abd.2023.06.006] [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: 04/05/2023] [Revised: 05/18/2023] [Accepted: 06/18/2023] [Indexed: 02/10/2024] Open
Abstract
BACKGROUND Psoriasis represents a chronic inflammatory phenotype shaped by genetic interactions, characterized by keratinocyte hyperproliferation and commonly affecting the skin and joints. Experimental and clinical studies suggest that the IL-17F gene locus plays a role as a central cytokine in the immunopathogenesis of psoriasis. OBJECTIVES Based on the central role of IL-17F in the pathogenesis of psoriasis, the authors thought that variations in this gene could affect the susceptibility and severity of this disease. Therefore, in this study, the authors aimed to analyze whether the IL-17F rs763780 variant has an effect on psoriasis pathogenesis in the Turkish population. METHOD In this case-control study, the study group consisted of 603 people (201 psoriasis patients (73 males/128 females)/402 controls (146 males/256 females) were genotyped in terms of IL-17F rs763780 polymorphism with TaqMan 5' Allelic Discrimination Test. RESULTS The genotype distributions of the IL-17F rs763780 polymorphism between patients and control groups were statistically different, and the TC (heterozygous genotype) and CC (homozygous mutant genotype) genotypes were more represented in the patients group than in the control group (24.9% vs. 10.2%; 2.0% vs. 0.2%, respectively). In addition, the variant C allele was higher in the patients group and this was statistically significant (p < 0.001), and the C allele carriage was associated with a 3.14-fold increased risk of psoriasis (95% CI 2.015‒24.921). STUDY LIMITATIONS The present study has some limitations. The first limitation is the relatively small sample size. The second limitation is that the authors could not measure IL-17F expression levels. However, the present study data draw attention to the importance of IL-17F which deserves to be studied in a larger sample group. CONCLUSION We report that IL-17F rs763780 TC and CC genotype and C allele are associated with an increased risk of psoriasis in the Turkish population.
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Affiliation(s)
| | - Burak Akşan
- Department of Skin Diseases, Giresun University, Faculty of Medicine, Giresun, Turkey
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Yang Y, Deng Y, Zhang G, Xu X, Xiong X, Yu S, Peng F, Tian X, Ye W, Chen H, Yu B, Liu Z, He X, Huang Z. α-mangostin derivatives ameliorated mouse DSS-induced chronic colitis via regulating Th17/Treg balance. Mol Immunol 2024; 166:110-118. [PMID: 38280829 DOI: 10.1016/j.molimm.2023.11.013] [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: 08/17/2023] [Revised: 11/08/2023] [Accepted: 11/22/2023] [Indexed: 01/29/2024]
Abstract
Th17 cell, an important subpopulation of helper T cell, plays an important role in the development of inflammatory bowel disease (IBD) and is thought to be a potential target for the treatment of IBD. In our previous study, we demonstrated that α-mangostin could relieve lupus nephritis via inhibiting Th17 cell function. In our preliminary study, we obtained four derivatives by adding chemical modification of α-mangostin which could also inhibit Th17 cell differentiation in vitro. In this study, we constructed a chronic IBD mouse model and demonstrated the therapeutic effects of α-mangostin and its derivatives as therapeutic agents for IBD. In compounds treating groups, intestinal inflammation showed significant improvement in symptoms which included weight loss, high disease activity index, colon length shorten and the change of intestinal flora. We also found that compounds could effectively either suppress the number of Th17 cell or increase the number of Treg cell detected by flow cytometry, thus reducing the Th17/Treg ratio and suppressing the level of intestinal inflammation. Notably, IL17-F levels, rather than IL17-A, were reduced in the colon of mice of compounds treating groups. Thus, α-mangostin and its derivatives ameliorate DSS-induced chronic colitis in mice by regulating Th17/Treg balance to alleviate intestinal inflammation and can modulate the intestinal microbial community. These results suggest that α-mangostin and its derivatives may be the new therapeutic option for chronic colitis.
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Affiliation(s)
- Yuying Yang
- Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China; Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, China.
| | - Yuqing Deng
- Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China; Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, China.
| | - Guoqiang Zhang
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China.
| | - Xiaoting Xu
- Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China; Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, China.
| | - Xiaoxiao Xiong
- Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China; Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, China.
| | - Si Yu
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China.
| | - Fanrong Peng
- Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China; Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, China.
| | - Xuyan Tian
- Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China; Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, China.
| | - Weiying Ye
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China.
| | - Huanpeng Chen
- Key Laboratory for Major Obstetric Diseases of Guangdong Province, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
| | - Bolan Yu
- Key Laboratory for Major Obstetric Diseases of Guangdong Province, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
| | - Zhonghua Liu
- Animal Experiment Center, South China Agricultural University, Guangzhou, China.
| | - Xixin He
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China.
| | - Zhaofeng Huang
- Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China; Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, China.
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Buran T, Batır MB, Çam FS, Kasap E, Çöllü F, Çelebi HBG, Şahin M. Molecular analyses of ADAMTS-1, -4, -5, and IL-17 a cytokine relationship in patients with ulcerative colitis. BMC Gastroenterol 2023; 23:345. [PMID: 37798683 PMCID: PMC10552413 DOI: 10.1186/s12876-023-02985-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Accepted: 10/02/2023] [Indexed: 10/07/2023] Open
Abstract
BACKGROUND Ulcerative colitis (UC) is a chronic inflammatory bowel disease that develops due to the impaired immune response in genetically susceptible individuals, and its etiopathogenesis is not fully elucidated. IL-17 A is a cytokine that is produced by a type of immune cell called Th17 cells and is involved in the immune response and inflammation. On the other hand, ADAMTS-1, -4, and - 5 are enzymes that are involved in the breakdown of extracellular matrix proteins, including proteoglycans, which are important components of the intestinal wall. This study aimed to evaluate the relationship between interleukin 17 (IL-17 A) cytokine, which plays a role in the pathogenesis of ulcerative colitis, and the inflammation-controlled a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-1, -4, and - 5 protein members. METHODS Bowel tissue samples and blood serum from 51 patients with UC and 51 healthy controls were included in this study. mRNA expression levels of the ADAMTS-1, -4, -5, and IL-17 A were analyzed by RT-qPCR, and immunohistochemical analyses were performed to evaluate ADAMTS-1, -4, -5, and IL-17 A proteins in tissue samples. In addition, ELISA analysis determined serum levels of the ADAMTS-1, -4, -5, and IL-17 A. RESULTS RT-qPCR results reveal that the expression of ADAMTS-1, -4, -5, and IL-17 A genes in the UC tissue samples were significantly high according to the control tissue samples. Also, ADAMTS-1, -4, -5, and IL-17 A proteins revealed enhanced expression pattern UC groups according to the control. Also, ADAMTS-1, -4, -5, and IL-17 A protein showed cytoplasmic localization patterns in both control and UC groups. The serum levels of ADAMTS-1,-5, and IL-17 A were significantly higher in UC samples than in the control group. CONCLUSIONS We observed a positive correlation between the ADAMTS-1, -5 and IL17A cytokine expression in UC samples. These results provide a new understanding of controlling crucial ADAMTS family protein members by IL-17 A cytokines with UC.
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Affiliation(s)
- Tahir Buran
- Department of Gastroenterology, Faculty of Medicine, Manisa Celal Bayar University, Manisa, Turkey.
| | - Muhammet Burak Batır
- Department of Biology, Faculty of Arts and Sciences, Manisa Celal Bayar University, Manisa, Turkey
| | - Fethi Sırrı Çam
- Department of Medical Genetics, Faculty of Medicine, Manisa Celal Bayar University, Manisa, Turkey
| | - Elmas Kasap
- Department of Gastroenterology, Faculty of Medicine, Manisa Celal Bayar University, Manisa, Turkey
| | - Fatih Çöllü
- Department of Biology, Faculty of Arts and Sciences, Manisa Celal Bayar University, Manisa, Turkey
| | | | - Mustafa Şahin
- Department of Internal Medicine, Faculty of Medicine, Manisa Celal Bayar University, Manisa, Turkey
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Zhang M, Peng L, Li W, Duan Y, Liu X, Chen S, Deng J, Liu X. IL12B and IL17 genes polymorphisms associated with differential susceptibility to juvenile idiopathic arthritis and juvenile-onset systemic lupus erythematosus in Chinese children. Medicine (Baltimore) 2023; 102:e34477. [PMID: 37543802 PMCID: PMC10403002 DOI: 10.1097/md.0000000000034477] [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: 05/09/2023] [Revised: 06/30/2023] [Accepted: 07/03/2023] [Indexed: 08/07/2023] Open
Abstract
Genetic factors play a crucial role in the immune response of juvenile idiopathic arthritis (JIA) and juvenile-onset systemic lupus erythematosus (JSLE). This study aimed to investigate the association of IL12B (rs3212227, rs6887695) and IL17 (rs2275913, rs763780) gene polymorphisms with the susceptibility of JIA and JSLE in Chinese children. A total of 303 healthy controls and 304 patients including 160 JIA and 144 patients were analyzed, and the genetic polymorphisms were genotyped by using a Sequenom MassArray system. There was a significant association between the IL12B rs3212227 genotype and the increased risk of JSLE (P = .01). For rs6887695, the minor allele C was significantly associated with the increased risk of JIA (odds ratio = 1.48, 95% confidence interval [CI] = 1.12-1.95, P = .005). Moreover, rs6887695 genotype was significantly associated with both JIA and JSLE susceptibility (P < .05). Besides, IL12B haplotype GC significantly associated with the increased risk of JIA (P = .016). However, no significant difference was found between the IL17 (rs2275913, rs763780) gene polymorphisms and JIA or JSLE susceptibility (P > .05). And similar genotype distributions of IL12B and IL17 polymorphisms were found between the patients with nephritis and without nephritis in JSLE (P > .05). Our results indicated that IL12B polymorphisms was associated with an increased risk for the development of JIA and JSLE in Chinese children, highlighting the involvement of inflammation in the pathogenesis of JIA and JSLE. Moreover, there was a risk haplotype in IL12B which could increase the risk of JIA.
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Affiliation(s)
- Menglan Zhang
- Department of Laboratory Medicine, West China Second University Hospital, Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China
| | - Leiwen Peng
- Department of Laboratory Medicine, West China Second University Hospital, Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China
| | - Wensheng Li
- Department of Laboratory Medicine, West China Second University Hospital, Sichuan University, Chengdu, China
| | - Yifei Duan
- Department of Laboratory Medicine, West China Second University Hospital, Sichuan University, Chengdu, China
| | - Xiaoqin Liu
- Department of Laboratory Medicine, West China Second University Hospital, Sichuan University, Chengdu, China
| | - Shasha Chen
- Department of Laboratory Medicine, West China Second University Hospital, Sichuan University, Chengdu, China
| | - Jiamin Deng
- Department of Laboratory Medicine, West China Second University Hospital, Sichuan University, Chengdu, China
| | - Xinle Liu
- Department of Laboratory Medicine, West China Second University Hospital, Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China
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Arıkan S, Öztürk O, Duygulu Ş, Atalay EÖ, Atalay A. Associations of IL-17 and IL-17 receptor polymorphisms with Behçet's disease in Denizli Province of Turkey. Immunol Res 2023; 71:600-608. [PMID: 36701075 DOI: 10.1007/s12026-023-09363-7] [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: 06/20/2022] [Accepted: 01/17/2023] [Indexed: 01/27/2023]
Abstract
Although the etiopathogenesis of Behçet's disease is not known, studies conducted in different populations show that it is a multifactorial disease that is thought to develop as a result of the interaction of environmental and genetic factors. IL-17 is thought to induce the neutrophilic inflammation and the tissue damage mediated by immune response in patients. Polymorphisms in the gene region encoding IL-17 and IL-17R molecules may play a critical role in the pathogenesis of the disease and contribute to the elucidation of disease mechanism. We aimed to show the association of IL-17A, IL-17F, and IL-17RC polymorphisms and haplotypes in Behçet's disease patients and its clinical features. We genotyped IL-17A (rs4711998 (A/G), rs8193036 (C/T), rs2275913 (A/G), rs3819025 (A/G), rs8193038 (A/G), rs3804513 (A/T), rs1974226 (C/T), rs3748067 (C/T)); IL-17F (rs763780 (T/C), rs2397084 (T/C)); and IL-17R (IL-17RC) (rs708567 (C/T)) polymorphisms in 88 patients with Behçet's disease and 133 healthy controls using PCR-RFLP-based approach. The results of our study showed that polymorphisms of IL-17A, rs8193036 (C/T), rs3819025 (G/A), rs3804513 (A/T), IL-17F rs2397084 (T/C), and IL-17RC rs708567 (C/T) are associated with the susceptibility to the BD. When the haplotype distributions of all loci of IL-17Aand IL-17A/IL-17F together were examined and in contrast to the data obtained from the controls, the GTGGAACC (27.84%) and GTGGAACCTT (25.57%) have the highest frequencies. In conclusion, the allele and genotype frequency differences of the IL-17A, IL-17F, and IL-17R and haplotype frequencies between Behçet's disease and controls indicate that the genetic structure of Behçet's disease may be different.
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Affiliation(s)
- Sanem Arıkan
- Department of Biophysics, Faculty of Medicine, Pamukkale University, 20070, Denizli, Turkey.
| | - Onur Öztürk
- Department of Biophysics, Faculty of Medicine, Malatya Turgut Özal University, Malatya, Turkey
| | - Şeniz Duygulu
- Department of Dermatology, Faculty of Medicine, Pamukkale University, Denizli, Turkey
| | - Erol Ömer Atalay
- Department of Biophysics, Faculty of Medicine, Pamukkale University, 20070, Denizli, Turkey
| | - Ayfer Atalay
- Department of Biophysics, Faculty of Medicine, Pamukkale University, 20070, Denizli, Turkey
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Zapata-Salazar NA, Kubelis-Lopez DE, Salinas-Santander MA, Sanchez-Dominguez CN, Xolalpa-Rosales AC, Gomez-Galindo ME, Ocampo-Candiani J. Association of rs4711998 of IL-17A, rs2275913 of IL-17A and rs763780 IL-17F gene polymorphisms with non-segmental vitiligo in a Mexican population. Arch Dermatol Res 2023; 315:447-454. [PMID: 35960353 DOI: 10.1007/s00403-022-02382-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Revised: 05/27/2022] [Accepted: 08/02/2022] [Indexed: 12/27/2022]
Abstract
Vitiligo is the most common depigmenting disease characterized by achromic macules due to selective loss of melanocytes. The pathogenesis remains poorly elucidated, and multiple hypotheses exist regarding its pathogenesis. Evidence suggests that stress on melanocytes can result in activation of the immune system, and involvement of both activated cluster of differentiation (CD8+) cytotoxic and CD4+ T cells in the dysfunction, depigmentation, and apoptosis of melanocytes. Recent studies show that the interleukin 17 (IL-17) axis plays a central role in the pathogenesis of the disease. IL-17 is an important regulatory effector cytokine in this pathway. The aim of this study was to evaluate the association of IL-17A rs4711998 (-832A/G), IL-17A rs2275913 (-197G/A), and IL-17F rs763780 (7488A/G) with vitiligo in a Northeastern Mexican population. This was a case-control study and included 116 patients with vitiligo and 116 control subjects. Genotype characterization of IL-17A rs4711998 (-832A/G), IL-17A rs2275913 (-197G/A), and IL-17F rs763780 (7488A/G) was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. A p ≤ 0.05 was considered significant. It was observed that the combination of the genotypes GG/GA for IL-17F rs763780 (7488A/G) was associated with an increased risk for the development of vitiligo (OR 2.0943, 95% Cl 1.2375-3.5445, p = 0.0056). Regarding IL-17A rs4711998 (-832A/G) and IL-17A rs2275913 (-197G/A) genotyping, no association with vitiligo development was found. In conclusion, the SNP rs763780 in the IL-17F gene appears to be a risk factor for vitiligo development in this Mexican population and it may be useful in future studies, especially for the development of new therapies.
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Affiliation(s)
- Natalia Aranza Zapata-Salazar
- Department of Dermatology, Facultad de Medicina y Hospital Universitario "Dr. Jose Eleuterio Gonzalez", Universidad Autonoma de Nuevo Leon (UANL), Av. Madero and Gonzalitos S/N, Mitras Centro, 64460, Monterrey, Nuevo Leon, Mexico
| | - David Emmanuel Kubelis-Lopez
- Department of Dermatology, Facultad de Medicina y Hospital Universitario "Dr. Jose Eleuterio Gonzalez", Universidad Autonoma de Nuevo Leon (UANL), Av. Madero and Gonzalitos S/N, Mitras Centro, 64460, Monterrey, Nuevo Leon, Mexico
| | | | - Celia Nohemi Sanchez-Dominguez
- Department of Biochemistry and Molecular Medicine, Facultad de Medicina y Hospital Universitario "Dr. Jose Eleuterio Gonzalez", Universidad Autonoma de Nuevo Leon (UANL), Monterrey, Nuevo Leon, Mexico
| | - Ana Cecilia Xolalpa-Rosales
- Facultad de Medicina y Hospital Universitario "Dr. Jose Eleuterio Gonzalez", Universidad Autonoma de Nuevo Leon (UANL), Monterrey, Nuevo Leon, Mexico
| | - Marely Eugenia Gomez-Galindo
- Facultad de Medicina y Hospital Universitario "Dr. Jose Eleuterio Gonzalez", Universidad Autonoma de Nuevo Leon (UANL), Monterrey, Nuevo Leon, Mexico
| | - Jorge Ocampo-Candiani
- Department of Dermatology, Facultad de Medicina y Hospital Universitario "Dr. Jose Eleuterio Gonzalez", Universidad Autonoma de Nuevo Leon (UANL), Av. Madero and Gonzalitos S/N, Mitras Centro, 64460, Monterrey, Nuevo Leon, Mexico.
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Jadeja SD, Vaishnav J, Bharti AH, Begum R. Elevated X-Box Binding Protein1 Splicing and Interleukin-17A Expression Are Associated With Active Generalized Vitiligo in Gujarat Population. Front Immunol 2022; 12:801724. [PMID: 35046957 PMCID: PMC8761938 DOI: 10.3389/fimmu.2021.801724] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Accepted: 12/13/2021] [Indexed: 11/18/2022] Open
Abstract
Vitiligo is an autoimmune skin disorder defined by the destruction of functional epidermal melanocytes. It is a multifactorial and polygenic disorder caused due to oxidative stress, endoplasmic reticulum (ER) stress, and autoimmunity, among other factors. In the present study, we aimed to investigate the association of X-box Binding Protein 1 (XBP1) and Interleukin-17A (IL-17A) polymorphisms and monitor their systemic as well as skin expression levels in vitiligo patients from Gujarat population in India. XBP1 rs2269577 G/C, IL17A rs2275913 G/A and IL17A rs8193036 C/T polymorphisms were genotyped by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method in 312 controls and 276 vitiligo patients. Transcript levels of spliced (sXBP1), unspliced XBP1 (uXBP1) and IL17A from peripheral blood mononuclear cells (PBMCs) as well as spliced and unspliced XBP1 from skin samples were analyzed by qPCR. IL-17A protein levels in suction-induced blister fluid (SBF) from the skin of study subjects were estimated by ELISA. The results revealed that genotype (p=0.010) and allele (p=0.014) frequencies of XBP1 rs2269577 G/C polymorphism were significantly different, however, no significant difference was observed in frequencies of IL17A rs2275913 G/A and IL17A rs8193036 C/T polymorphisms in control and patient population. Gene expression analysis revealed that sXBP1 and IL17A levels were significantly higher in PBMCs of generalized (p=0.030 and p=0.039, respectively) and active (p=0.024 and p=0.017, respectively) vitiligo patients. Moreover, we observed a significantly elevated sXBP1 expression (p=0.037) as well as IL-17A protein levels (p=0.009) in perilesional skin of vitiligo patients as compared to controls. Overall, these findings suggest XBP1 and IL17A play an important role in vitiligo and further substantiate the involvement of ER stress in exacerbating immune-mediated vitiligo pathogenesis.
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Affiliation(s)
- Shahnawaz D Jadeja
- Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, India
| | - Jayvadan Vaishnav
- Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, India
| | - Ankit H Bharti
- Dermatology Department, Dr. Ankit's Dermatopathology Research Centre, Vyara, India
| | - Rasheedunnisa Begum
- Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, India
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Xiang Z, Hao Z, Cui P, Lin L, Chen M, Chen PM. Association between interleukin-17F rs763780 polymorphism and psoriasis risk: A meta-analysis. Indian J Dermatol Venereol Leprol 2021; 88:150-155. [PMID: 34877855 DOI: 10.25259/ijdvl_1401_20] [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] [Received: 12/01/2020] [Accepted: 07/01/2021] [Indexed: 12/14/2022]
Abstract
BACKGROUND The polymorphism of interleukin-17F rs763780 has been found to have a probable association with increased risk of developing psoriasis. AIMS This study aims to get a more convincing estimation of the association between the interleukin-17F rs763780 T /C polymorphism and psoriasis risk. METHODS Two authors independently searched the databases including PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, Wanfang and Chinese Biomedical Literature Databases for case-control studies which reported the odds ratios with 95% confidence intervals comparing genotype and allele frequencies of the interleukin-17F rs763780 polymorphism in patients with psoriasis versus participants without psoriasis. RESULTS A total of seven case-control studies incorporating 1824 cases and 1585 controls were identified. The pooled odds ratios indicated that interleukin-17F rs763780 C allele was a risk factor for psoriasis in allele frequency, recessive model and homozygote model (P < 0.05). Subgroup analysis by ethnicity further indicated that the C allele was closely related to increased risk of psoriasis in Asian populations (P < 0.05), but not in Caucasians. LIMITATIONS Only a few studies on the interleukin-17F rs763780 polymorphism in psoriasis have been reported till date, thus the data is insufficient. Only one gene polymorphic site was selected for this study, and it is not clear whether other genetic mutation functional sites affect the gene. Further studies on confounding effects of other genetic polymorphisms are needed. CONCLUSION The present meta-analysis results suggested that the interleukin-17F rs763780 T /C is significantly associated with psoriasis risk in Asians.
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Affiliation(s)
- Zhi Xiang
- Department of Dermatology, Institute of Dermatology, Chinese Academy of Medical Science and Peking Union Medical College, Nanjing, Jiangsu, China
| | - Zhimin Hao
- Department of Dermatology, Institute of Dermatology, Chinese Academy of Medical Science and Peking Union Medical College, Nanjing, Jiangsu, China
| | - Pangen Cui
- Department of Dermatology, Institute of Dermatology, Chinese Academy of Medical Science and Peking Union Medical College, Nanjing, Jiangsu, China
| | - Lin Lin
- Department of Dermatology, Institute of Dermatology, Chinese Academy of Medical Science and Peking Union Medical College, Nanjing, Jiangsu, China
| | - Min Chen
- Department of Dermatology, Institute of Dermatology, Chinese Academy of Medical Science and Peking Union Medical College, Nanjing, Jiangsu, China
| | - Pro Min Chen
- Department of Dermatology, Institute of Dermatology, Chinese Academy of Medical Science and Peking Union Medical College, Nanjing, Jiangsu, China
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11
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Ismail AM, Higazi AM, Nomeir HM, Farag NM. IL-23/Th17 pathway and IL-17A gene polymorphism in Egyptian children with immune thrombocbytopenic purpura. Ital J Pediatr 2021; 47:178. [PMID: 34446083 PMCID: PMC8394206 DOI: 10.1186/s13052-021-01131-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Accepted: 08/13/2021] [Indexed: 11/25/2022] Open
Abstract
Background Immune thrombocytopenic purpura (ITP) is an acquired complex autoimmune thrombocytopenia. Uncontrolled cellular immune response is one of the key triggers for the loss of immune tolerance in ITP patients. The purpose of this study was to investigate the association of IL-23/Th17, IL-17A and IL-17A rs2275913 gene polymorphism with ITP in Egyptian children. Methods 60 patients with ITP and 50 healthy control children from Minia city- Egypt were involved. Serum levels of IL-23 and IL-17A were determined by enzyme-linked immunosorbent assay. The frequency of Th17 cells was measured using flow cytometer. Genotyping for IL-17A was performed via polymerase chain reaction-restriction fragment length polymorphism. Results Comparing children with ITP to controls, serum levels of IL-23 and IL-17A as well as Th17 cells percentage were significantly increased (p < 0.001). Also, higher levels of these ILs and Th17 cells percentage were associated with decreased platelet count within ITP patients (p < 0.001). Analysis of genotype frequencies for IL-17A rs2275913 polymorphism and its alleles (A, G) showed no significant difference between cases and controls. Likewise, no significant differences were demonstrated between acute and chronic ITP regarding both IL-17A rs2275913 polymorphism prevalence and levels of IL-23, IL-17A plus Th17 cells percentage. The frequency of A alleles was 85 and 86% within patients and controls, respectively. Conclusions Elevated levels of IL-23, IL-17A and Th17 cells may be involved in ITP pathogenesis while IL-17A polymorphism rs2275913 is not prevalent in Egyptian children with ITP.
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Affiliation(s)
- Ahlam M Ismail
- Minia Maternity and Children University Hospital, Pediatrics department, Faculty of Medicine, Minia University, Minia, Egypt.
| | - Aliaa M Higazi
- Clinical and Chemical Pathology department, Faculty of Medicine, Minia University, Minia, Egypt
| | - Hanan M Nomeir
- Medical Biochemistry department, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Naglaa M Farag
- Clinical and Chemical Pathology department, Faculty of Medicine, Minia University, Minia, Egypt
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12
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Rapolu BL, Pullagurla A, Ganta S, Komaravalli PL, Gaddam SL. Immuno‐genetic importance of Th17 in susceptibility to TB. Scand J Immunol 2021. [DOI: 10.1111/sji.13085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Affiliation(s)
| | - Ashwini Pullagurla
- Department of Genetics & Biotechnology Osmania University Hyderabad India
- Bhagwan Mahavir Medical Research Centre, Masab Tank Hyderabad India
| | - Soujanya Ganta
- Department of Genetics & Biotechnology Osmania University Hyderabad India
| | | | - Suman Latha Gaddam
- Department of Genetics & Biotechnology Osmania University Hyderabad India
- Bhagwan Mahavir Medical Research Centre, Masab Tank Hyderabad India
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13
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Noviello D, Mager R, Roda G, Borroni RG, Fiorino G, Vetrano S. The IL23-IL17 Immune Axis in the Treatment of Ulcerative Colitis: Successes, Defeats, and Ongoing Challenges. Front Immunol 2021; 12:611256. [PMID: 34079536 PMCID: PMC8165319 DOI: 10.3389/fimmu.2021.611256] [Citation(s) in RCA: 71] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Accepted: 04/26/2021] [Indexed: 12/13/2022] Open
Abstract
Ulcerative colitis (UC) is a chronic relapsing disorder of the colonic tract, characterized by a dysregulated innate and adaptive immune response to gut microbiota that contributes to the perpetuation of intestinal inflammatory processes. The Interleukin (IL) 23/IL17 axis has been reported to play a key role in UC pathogenesis promoting Th17 cells and cytokines-related immune response. Recently, the blockade of IL23/IL17 pathways has been raised enormous interest in the treatment o several chronic inflammatory disorders. In this review, we summarize the emerging results from clinical trials that evoked both promise and discouragement in IL23/IL17 axis in the treatment of UC. Targeting IL23 p40 through Ustekinumab results safe and effective to induce and maintain clinical remission, low inflammatory indexes, mucosal healing, and a better quality of life. Studies targeting IL23 p19 through Mirikizumab, Risankizumab, Brazikumab and Guselkumab are still ongoing. To date, no clinical studies targeting IL17 pathway are ongoing in UC. IL-17 targeting is thought to have a context-dependent biological effect, based on whether cytokine is selectively targeted or if its function is dampened by the upstream block of IL23.
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MESH Headings
- Animals
- Antibodies, Monoclonal/pharmacology
- Antibodies, Monoclonal/therapeutic use
- Antibodies, Monoclonal, Humanized/pharmacology
- Antibodies, Monoclonal, Humanized/therapeutic use
- Colitis, Ulcerative/diagnosis
- Colitis, Ulcerative/drug therapy
- Colitis, Ulcerative/immunology
- Colitis, Ulcerative/metabolism
- Disease Management
- Disease Susceptibility
- Gastrointestinal Microbiome/drug effects
- Gastrointestinal Microbiome/immunology
- Humans
- Immunomodulation/drug effects
- Interleukin-17/metabolism
- Interleukin-23/metabolism
- Molecular Targeted Therapy
- Signal Transduction/drug effects
- Treatment Outcome
- Ustekinumab/pharmacology
- Ustekinumab/therapeutic use
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Affiliation(s)
- Daniele Noviello
- Institute of Life Sciences, Scuola Superiore Sant’Anna, Pisa, Italy
| | - Riccardo Mager
- Inflammatory Bowel Disease (IBD) Center, Laboratory of Gastrointestinal Immunopathology, Humanitas Clinical and Research Center-IRCCS, Rozzano, Italy
| | - Giulia Roda
- Inflammatory Bowel Disease (IBD) Center, Laboratory of Gastrointestinal Immunopathology, Humanitas Clinical and Research Center-IRCCS, Rozzano, Italy
- Inflammatory Bowel Disease (IBD) Center, Department of Gastroenterology, Humanitas Clinical and Research Center-IRCCS, Rozzano, Italy
| | - Riccardo G. Borroni
- Inflammatory Bowel Disease (IBD) Center, Department of Gastroenterology, Humanitas Clinical and Research Center-IRCCS, Rozzano, Italy
- Dermatology, Humanitas Clinical and Research Center-IRCCS, Rozzano, Italy
| | - Gionata Fiorino
- Inflammatory Bowel Disease (IBD) Center, Laboratory of Gastrointestinal Immunopathology, Humanitas Clinical and Research Center-IRCCS, Rozzano, Italy
- Inflammatory Bowel Disease (IBD) Center, Department of Gastroenterology, Humanitas Clinical and Research Center-IRCCS, Rozzano, Italy
| | - Stefania Vetrano
- Inflammatory Bowel Disease (IBD) Center, Laboratory of Gastrointestinal Immunopathology, Humanitas Clinical and Research Center-IRCCS, Rozzano, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
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14
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Agonia I, Couras J, Cunha A, Andrade AJ, Macedo J, Sousa-Pinto B. IL-17, IL-21 and IL-22 polymorphisms in rheumatoid arthritis: A systematic review and meta-analysis. Cytokine 2020; 125:154813. [PMID: 31454755 DOI: 10.1016/j.cyto.2019.154813] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2018] [Revised: 07/07/2019] [Accepted: 08/12/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND Rheumatoid Arthritis (RA) is an autoimmune systemic disease and in its pathogenesis participate several proinflammatory cytokines, including those produced by Th17 cells. We performed a systematic review aiming to assess the associations between polymorphisms in Th17 cytokines, namely IL-17A, IL-17F, IL-21 and IL-22, and susceptibility to RA. METHODS We searched three electronic databases (MEDLINE, Scopus and Web of Science) for observational studies assessing the association between susceptibility to RA (or its clinical presentation) and polymorphisms of the cytokines IL-17A, IL-17F, IL-21 and IL-22. From the selected studies, we extracted information on the studied polymorphisms, assessed outcomes, and demographic characteristics of participants. We performed random effects meta-analyses assessing the associations between susceptibility to RA and different genotypes of the IL-17A rs2275913, IL-17Frs763780 andIL-17Frs2397084polymorphisms. Primary studies' quality was assessed using the Q-Genie tool. RESULTS Fifteen studies were included in this systematic review. Five IL-17A polymorphisms were reported to be associated with susceptibility to RA. For the IL-17A rs2275913 polymorphism, our meta-analysis showed the AA genotype to be significantly associated with lower susceptibility to RA(OR = 0.76; 95%CI = 0.61-0.93;p = 0.01), while the opposite was observed for the GG genotype (OR = 1.20; 95%CI = 1.06-1.35;p = 0.01). Concerning IL-17Frs763780 polymorphism, theTT genotype was found to be significantly less frequent in RA patients(OR = 0.49; 95%CI = 0.31-0.77;p = 0.002), while the opposite was observed for the CT genotype (OR = 2.00; 95%CI = 1.03-3.87;p = 0.04). No significant associations were found regarding rs2397084polymorphisms. For IL-21, rs6822844 and rs4505848 were described to have significant associations with susceptibility to RA. No studies were found assessing IL-22 polymorphisms in RA. CONCLUSIONS IL-17A rs2275913 and IL-17F rs763780 polymorphisms are significantly associated with susceptibility to RA and with different clinical characteristics of this disease.
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Affiliation(s)
- Inês Agonia
- Basic and Clinical Immunology Unit, Department of Pathology, Faculty of Medicine of the University of Porto, Porto, Portugal.
| | - Juliana Couras
- Basic and Clinical Immunology Unit, Department of Pathology, Faculty of Medicine of the University of Porto, Porto, Portugal; Department of Physics, University of Aveiro, Aveiro, Portugal
| | - Anita Cunha
- Basic and Clinical Immunology Unit, Department of Pathology, Faculty of Medicine of the University of Porto, Porto, Portugal
| | - Alda João Andrade
- Basic and Clinical Immunology Unit, Department of Pathology, Faculty of Medicine of the University of Porto, Porto, Portugal
| | - Juliana Macedo
- Basic and Clinical Immunology Unit, Department of Pathology, Faculty of Medicine of the University of Porto, Porto, Portugal
| | - Bernardo Sousa-Pinto
- Basic and Clinical Immunology Unit, Department of Pathology, Faculty of Medicine of the University of Porto, Porto, Portugal; MEDCIDS-Department of Community Medicine, Information and Health Decision Sciences, Faculty of Medicine, University of Porto, Porto, Portugal; CINTESIS-Center for Health Technology and Services Research, Porto, Portugal
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15
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Choi BG, Hong JY, Hong JR, Hur MS, Kim SM, Lee YW, Choe YB, Ahn KJ. The IL17F His161Arg polymorphism, a potential risk locus for psoriasis, increases serum levels of interleukin-17F in an Asian population. Sci Rep 2019; 9:18921. [PMID: 31831764 PMCID: PMC6908672 DOI: 10.1038/s41598-019-55062-5] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Accepted: 11/22/2019] [Indexed: 02/08/2023] Open
Abstract
Interleukin 17 (IL-17) plays pivotal role in the pathogenesis of psoriasis. In a previous study, we identified a locus in the IL17F gene that is associated with psoriasis, the IL17F rs763780 (His161Arg) T/C variant. The current study aimed to elucidate the association between this polymorphism and psoriasis, and to determine its effect on serum levels of cytokine. A total of 116 psoriasis patients and 97 healthy volunteers were recruited. Genotyping analysis was performed using quantitative polymerase chain reaction, and serum levels of cytokine were measured using a multiplex immunoassay. The IL17F His161Arg polymorphism was significantly associated with psoriasis based on the genotype and allele analyses. Psoriasis patients harbouring the mutant allele had significantly increased serum levels of IL-17F. Our results suggest that this polymorphism is a potential risk locus for psoriasis and that it results in a direct increase in IL-17F production.
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Affiliation(s)
- Byung Gon Choi
- Department of Dermatoogy, Konkuk University School of Medicine, Seoul, Korea
| | - Ji Youn Hong
- Department of Dermatoogy, Konkuk University School of Medicine, Seoul, Korea
| | - Joo Ran Hong
- Department of Dermatoogy, Konkuk University School of Medicine, Seoul, Korea
| | - Min Seok Hur
- Department of Dermatoogy, Konkuk University School of Medicine, Seoul, Korea
| | - Sung Min Kim
- Department of Dermatoogy, Konkuk University School of Medicine, Seoul, Korea
| | - Yang Won Lee
- Department of Dermatoogy, Konkuk University School of Medicine, Seoul, Korea.,Research Institute of Medical Science, Konkuk University School of medicine, Seoul, Korea
| | - Yong Beom Choe
- Department of Dermatoogy, Konkuk University School of Medicine, Seoul, Korea. .,Research Institute of Medical Science, Konkuk University School of medicine, Seoul, Korea.
| | - Kyu Joong Ahn
- Department of Dermatoogy, Konkuk University School of Medicine, Seoul, Korea.,Research Institute of Medical Science, Konkuk University School of medicine, Seoul, Korea
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16
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Kurnaz S, Yazici AB, Nursal AF, Cetinay Aydin P, Ongel Atar A, Aydin N, Kincir Z, Pehlivan S. CNR2 rs2229579 and COMT Val158Met variants, but not CNR2 rs2501432, IL-17 rs763780 and UCP2 rs659366, contribute to susceptibility to substance use disorder in the Turkish population. PSYCHIAT CLIN PSYCH 2019. [DOI: 10.1080/24750573.2019.1688030] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/25/2022] Open
Affiliation(s)
- Selin Kurnaz
- Department of Medical Biology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Ahmet Bulent Yazici
- Department of Psychiatry, Sakarya University Training and Research Hospital, Sakarya, Turkey
| | - Ayse Feyda Nursal
- Department of Medical Genetics, Faculty of Medicine, Hitit University, Corum, Turkey
| | - Pinar Cetinay Aydin
- Department of Psychiatry, Bakirkoy Mazhar Osman Training and Research Hospital for Psychiatry, Istanbul, Turkey
| | - Ayca Ongel Atar
- Department of Psychiatry, Bakirkoy Mazhar Osman Training and Research Hospital for Psychiatry, Istanbul, Turkey
| | - Nazan Aydin
- Department of Psychiatry, Bakirkoy Mazhar Osman Training and Research Hospital for Psychiatry, Istanbul, Turkey
| | - Zeliha Kincir
- Department of Psychiatry, Bakirkoy Mazhar Osman Training and Research Hospital for Psychiatry, Istanbul, Turkey
| | - Sacide Pehlivan
- Department of Medical Biology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
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17
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Subbanna M, Shivakumar V, Talukdar PM, Narayanaswamy JC, Venugopal D, Berk M, Varambally S, Venkatasubramanian G, Debnath M. Role of IL-6/RORC/IL-22 axis in driving Th17 pathway mediated immunopathogenesis of schizophrenia. Cytokine 2018; 111:112-118. [PMID: 30138899 DOI: 10.1016/j.cyto.2018.08.016] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2018] [Revised: 08/01/2018] [Accepted: 08/13/2018] [Indexed: 02/07/2023]
Abstract
The immuno-inflammatory origin of schizophrenia in a subset of patients is viewed as a key element of an overarching etiological construct. Despite substantial research, the immune components exerting major effect are yet to be fully clarified. Disrupted T cell networks have consistently been linked to the pathogenesis of schizophrenia. Amongst the Th cell subsets, the Th17 cells have emerged as a paradigmatic lineage with significant functional implications in a vast number of immune mediated diseases including brain disorders such as schizophrenia. The present study was aimed at examining the functional role of the Th17 pathway in schizophrenia. To address this, genotyping of IL17A (rs2275913; G197A) Single Nucleotide Polymorphism was carried out by the PCR-RFLP method in 221 schizophrenia patients and 223 healthy control subjects. Gene expression of two transcription factors STAT3 and RORC was quantified in a subset of drug naïve schizophrenia patients (n = 56) and healthy controls (n = 52) by TaqMan assay. The plasma levels of fifteen cytokines belonging to Th17 pathway were estimated in a subset of drug naïve schizophrenia patients (n = 61) and healthy controls (n = 50) by using Bio-Plex Pro Human Th17 cytokine assays. The AA genotype was associated with higher total score of bizarre behaviour and apathy in female schizophrenia patients. A high gene expression level of RORC was observed in drug naïve schizophrenia patients. In addition, significantly elevated plasma levels of IL-6 and IL-22, and reduced levels of IL-1β and IL-17F were noted in schizophrenia patients. Taken together, these findings indicate a dysregulated Th17 pathway in schizophrenia patients.
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Affiliation(s)
- Manjula Subbanna
- Department of Human Genetics, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India; Translational Psychiatry Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India
| | - Venkataram Shivakumar
- Translational Psychiatry Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India; Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India
| | - Pinku Mani Talukdar
- Department of Human Genetics, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India
| | - Janardhanan C Narayanaswamy
- Translational Psychiatry Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India; Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India
| | - Deepthi Venugopal
- Department of Human Genetics, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India; Translational Psychiatry Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India
| | - Michael Berk
- Deakin University, School of Medicine, IMPACT Strategic Research Centre, Geelong, Victoria, Australia; Orygen, The Centre of Excellence in Youth Mental Health, The Department of Psychiatry and the Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Australia
| | - Shivarama Varambally
- Translational Psychiatry Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India; Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India
| | - Ganesan Venkatasubramanian
- Translational Psychiatry Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India; Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India
| | - Monojit Debnath
- Department of Human Genetics, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India.
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18
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Cho YA, Lee J, Oh JH, Chang HJ, Sohn DK, Shin A, Kim J. Inflammatory Dietary Pattern, IL-17F Genetic Variant, and the Risk of Colorectal Cancer. Nutrients 2018; 10:nu10060724. [PMID: 29874787 PMCID: PMC6024771 DOI: 10.3390/nu10060724] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2018] [Revised: 05/22/2018] [Accepted: 05/31/2018] [Indexed: 12/17/2022] Open
Abstract
A proinflammatory diet may increase the risk of colorectal cancer, but its role may differ according to individuals’ genetic variants. We aimed to examine whether a specific dietary pattern reflecting inflammation was associated with a risk of colorectal cancer and whether IL-17F genetic variant altered this association. In a study of 695 colorectal cancer cases and 1846 controls, we derived a reduced rank regression dietary pattern using 32 food groups as predictors and the plasma C-reactive protein (CRP) concentration as the response. High CRP levels were associated with a high risk of colorectal cancer (OR (95% CI) = 3.58 (2.65–4.82) for the highest quartile vs. lowest quartile). After adjusting for potential confounding factors, high pattern scores were associated with a high risk of colorectal cancer (OR (95% CI) = 9.98 (6.81–14.62) for the highest quartile vs. lowest quartile). When stratified by the IL-17F rs763780 genotype, this association was stronger for individuals carrying the C allele (p for interaction = 0.034), particularly for individuals with rectal cancer (p for interaction = 0.011). In conclusion, a dietary pattern reflecting inflammation was significantly associated with colorectal cancer risk. Moreover, this association could be modified according to the IL-17F rs763780 genotype and anatomic site.
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Affiliation(s)
- Young Ae Cho
- Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang 10408, Gyeonggi-do, Korea.
| | - Jeonghee Lee
- Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang 10408, Gyeonggi-do, Korea.
| | - Jae Hwan Oh
- Center for Colorectal Cancer, National Cancer Center Hospital, National Cancer Center, Goyang 10408, Gyeonggi-do, Korea.
| | - Hee Jin Chang
- Center for Colorectal Cancer, National Cancer Center Hospital, National Cancer Center, Goyang 10408, Gyeonggi-do, Korea.
| | - Dae Kyung Sohn
- Center for Colorectal Cancer, National Cancer Center Hospital, National Cancer Center, Goyang 10408, Gyeonggi-do, Korea.
| | - Aesun Shin
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul 03080, Korea.
| | - Jeongseon Kim
- Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang 10408, Gyeonggi-do, Korea.
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19
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Gueiros LA, Arão T, Souza T, Vieira CL, Gomez RS, Almeida OP, Lodi G, Leão JC. IL17A polymorphism and elevated IL17A serum levels are associated with oral lichen planus. Oral Dis 2017; 24:377-383. [DOI: 10.1111/odi.12718] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2016] [Revised: 07/06/2017] [Accepted: 07/10/2017] [Indexed: 12/13/2022]
Affiliation(s)
- LA Gueiros
- Centro de Ensino e Pesquisa de Laser em Odontologia - CEPLO; Programa de Pós-graduação em Odontologia; Universidade Federal de Pernambuco; Recife Brazil
| | - T Arão
- Departamento de Cirurgia Oral e Patologia; Faculdade de Odontologia; Universidade Federal de Minas Gerais; Belo Horizonte Brazil
| | - T Souza
- Centro de Ensino e Pesquisa de Laser em Odontologia - CEPLO; Programa de Pós-graduação em Odontologia; Universidade Federal de Pernambuco; Recife Brazil
| | - CL Vieira
- Centro de Ensino e Pesquisa de Laser em Odontologia - CEPLO; Programa de Pós-graduação em Odontologia; Universidade Federal de Pernambuco; Recife Brazil
| | - RS Gomez
- Departamento de Cirurgia Oral e Patologia; Faculdade de Odontologia; Universidade Federal de Minas Gerais; Belo Horizonte Brazil
| | - OP Almeida
- Área de Patologia; Faculdade de Odontologia de Piracicaba; Universidade Estadual de Campinas; Piracicaba Brazil
| | - G Lodi
- Oral Medicine Unit; Dipartimento di Scienze Biomediche, Chirurgiche e Odontoiatriche; Università degli Studi di Milano; Milan Italy
| | - JC Leão
- Centro de Ensino e Pesquisa de Laser em Odontologia - CEPLO; Programa de Pós-graduação em Odontologia; Universidade Federal de Pernambuco; Recife Brazil
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20
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Hassani E, Bagheri M, Rad IA, Mohebbi I. Association between SNPs at IL-17A and IL-17F and susceptibility to accelerated silicosis. Toxicol Ind Health 2017; 33:673-680. [PMID: 28481151 DOI: 10.1177/0748233717695431] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/08/2025]
Abstract
The association between single nucleotide polymorphisms (SNPs) in the interleukin (IL)-17 gene and silicosis has been evaluated in different populations. The aim of the present study was to analyze the association between SNPs at IL-17A (-832A/G) and IL-17F (+7488A/G) and susceptibility to accelerated silicosis in the Iranian Kurdish population. We studied 48 patients with accelerated silicosis and 62 controls. Genomic DNA was isolated using the "salting out" method. PCR-RFLP was performed for all SNPs typing. The frequencies of A/A, A/G, and G/G genotypes at IL-17A (-832A/G) were 4 (8.33%), 23 (47.92%), and 21 (43.75%) in patients and 5 (8.06%), 35 (56.45%), and 22 (35.48%) in controls, respectively. The frequencies of A and G alleles at IL-17 (-832A/G) were 31 (32.29%) and 65 (67.71%) in patients, and 45 (36.29%) and 79 (63.71%) in the controls, respectively. The frequencies of A/A, A/G, and G/G genotypes at IL-17F (+7488A/G) were 1 (2.08%), 47 (97.92%), and 0 (0%) in patients, and 11 (17.74%), 51 (82.26%), and 0 (0%) in the controls, respectively. The frequencies of A and G alleles at IL-17F (+7488A/G) were 49 (51.04%) and 47 (48.96%) in patients, and 73 (58.87%) and 51 (41.13%) in the controls, respectively. IL-17F (+7488A/G) genotype was more frequent among the cases compared with controls (97.92% vs. 82.26%). The frequency of the IL-17F (+7488A/G) genotype was significantly greater in patients with accelerated silicosis (odds ratio = 10.13 95%; confidence interval = 1.2-81.5; p = 0.008). The IL-17F (+7488A/G) genotype revealed a significantly increased risk of accelerated silicosis ( p < 0.05). The IL-17F (+7488 G) allele was associated with an increased risk of accelerated silicosis, but in the case of the IL-17A (-832A/G) polymorphism, a significant association was not observed.
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Affiliation(s)
- Ebrahim Hassani
- 1 Department of Anesthesiology, Urmia University of Medical Sciences, Urmia, Iran
| | - Morteza Bagheri
- 2 Cellular and Molecular Research Center, Department of Genetics, Urmia University of Medical Sciences, Urmia, Iran
| | - Isa Abdi Rad
- 2 Cellular and Molecular Research Center, Department of Genetics, Urmia University of Medical Sciences, Urmia, Iran
| | - Iraj Mohebbi
- 3 Social Determinants of Health Research Center, Department of Occupational Medicine, Urmia University of Medical Sciences, Urmia, Iran
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21
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Neco HVPC, Teixeira VGS, Trindade ACL, Magalhães PMR, Lorena VMB, Vasconcelos LR, Moura PMMF, Morais CNL. IL17A Polymorphism Is Not Associated with Human T-Lymphotropic Virus 1-Associated Myelopathy/Tropical Spastic Paraparesis. Viral Immunol 2017; 30:298-301. [PMID: 28410448 DOI: 10.1089/vim.2016.0152] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
The human T-lymphotropic virus 1 (HTLV-1) is the causative agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The present study investigated the association between the rs2275913 polymorphism in the IL17A gene and the development of HAM/TSP. Peripheral blood samples were collected from 116 patients (29 symptomatic patients with HAM/TSP and 87 asymptomatic) with a positive diagnosis of HTLV-1. The single nucleotide polymorphism genotyping was carried out by real time PCR using TaqMan probes. In addition, serum levels of IL-2, IFN-γ, TNF-α, IL-4, IL-6, IL-10, and IL-17 were measured in 64 infected individuals from the study (47 asymptomatic and 17 HAM/TSP), using cytometric bead array technique. No significant differences were found in genotypic and allelic frequencies between the groups. Analysis of cytokine levels showed highest concentrations of IFN-γ and TNF-α in HAM/TSP patients. The results of the present study, therefore, suggest a lack of association between the rs2275913 polymorphism in the IL17A gene and the presence of HAM/TSP.
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Affiliation(s)
- Heytor V P C Neco
- 1 Department of Virology, Centro de Pesquisas Aggeu Magalhães (CPqAM) Research Center , Fundação Oswaldo Cruz (Fiocruz), Recife, Brazil
| | - Vanessa G S Teixeira
- 2 Instituto de Ciências Biológicas (ICB), Universidade de Pernambuco , Recife, Brazil
| | - Ana C L Trindade
- 2 Instituto de Ciências Biológicas (ICB), Universidade de Pernambuco , Recife, Brazil
| | | | - Virgínia M B Lorena
- 4 Department of Immunology, Centro de Pesquisas Aggeu Magalhães (CPqAM) Research Center , Fundação Oswaldo Cruz (Fiocruz), Recife, Brazil
| | - Luydson R Vasconcelos
- 5 Department of Parasitology, Centro de Pesquisas Aggeu Magalhães (CPqAM) Research Center , Fundação Oswaldo Cruz (Fiocruz), Recife, Brazil
| | - Patricia M M F Moura
- 2 Instituto de Ciências Biológicas (ICB), Universidade de Pernambuco , Recife, Brazil
| | - Clarice N L Morais
- 1 Department of Virology, Centro de Pesquisas Aggeu Magalhães (CPqAM) Research Center , Fundação Oswaldo Cruz (Fiocruz), Recife, Brazil
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22
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Ren W, Wu Z, Ma R, Liu Z, Wang Y, Wu L, Liu S, Wang Z. Polymorphisms in the IL-17 Gene (rs2275913 and rs763780) Are Associated with Hepatitis B Virus Infection in the Han Chinese Population. Genet Test Mol Biomarkers 2017; 21:286-291. [PMID: 28277785 DOI: 10.1089/gtmb.2016.0177] [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] [Indexed: 01/11/2023] Open
Abstract
AIM Interleukin-17 (IL-17) can accelerate the release of many pro-inflammatory cytokines. The purpose of our study was to investigate the potential association between polymorphisms in the IL-17 gene and susceptibility to hepatitis B virus (HBV) infection in the Han Chinese population. METHODS We recruited 596 HBV-infected patients and 612 ethnically matched controls, who were then genotyped for the IL-17A and IL-17F polymorphisms, rs2275913 and rs763780, respectively, by using TaqMan probe-based real-time polymerase chain reaction. The frequencies of the alleles and genotypes in patients and controls were compared by the χ2 test. RESULTS Statistically significant differences in genotypic and allelic frequencies were revealed at both polymorphic sites between HBV-positive patients and controls (rs2275913: genotype χ2 = 37.74, p < 0.001 and allele χ2 = 22.17, p < 0.001, odds ratio [OR] = 0.654, 95% confidence interval [CI] = 0.548-0.781. rs763780: genotype χ2 = 19.80, p < 0.001 and allele χ2 = 18.78, p < 0.001, OR = 0.507, 95% CI = 0.371-0.692). CONCLUSIONS These results indicate that the IL-17A rs2275913 and IL-17F rs763780 polymorphisms are associated with HBV infection in the Han Chinese population. We conclude that possession of the GG genotype and the G allele at rs2275913, and the TT genotype and the T allele at rs763780 might increase the risk of HBV infection. Larger-scale, multiracial studies are necessary to evaluate the role of IL-17 polymorphisms in relation to an enhanced risk of HBV infection.
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Affiliation(s)
- Wei Ren
- 1 Shandong Provincial Key Laboratory of Metabolic Disease, The Affiliated Hospital of Qingdao University , Qingdao, China
| | - Zehua Wu
- 2 Department of Hepatobiliary Surgery, The Affiliated Hospital of Qingdao University , Qingdao, China
| | - Ruixin Ma
- 3 Department of Endocrinology, The Affiliated Hospital of Qingdao University , Qingdao, China
| | - Zhen Liu
- 1 Shandong Provincial Key Laboratory of Metabolic Disease, The Affiliated Hospital of Qingdao University , Qingdao, China
| | - Yingying Wang
- 4 Department of Dermatology, The Affiliated Hospital of Qingdao University , Qingdao, China
| | - Liqun Wu
- 2 Department of Hepatobiliary Surgery, The Affiliated Hospital of Qingdao University , Qingdao, China
| | - Shiguo Liu
- 5 Prenatal Diagnosis Center, The Affiliated Hospital of Qingdao University , Qingdao, China
| | - Zusen Wang
- 2 Department of Hepatobiliary Surgery, The Affiliated Hospital of Qingdao University , Qingdao, China
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23
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Tian J, Liu Y, Jiang Y, Zhou H, Zhu T, Zhao X, Peng L, Yan C. Association of single nucleotide polymorphisms of IL23R and IL17 with necrotizing enterocolitis in premature infants. Mol Cell Biochem 2017; 430:201-209. [PMID: 28224332 DOI: 10.1007/s11010-017-2972-6] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2016] [Accepted: 02/02/2017] [Indexed: 12/30/2022]
Abstract
Necrotizing enterocolitis (NEC) is a severe gastrointestinal inflammatory disease in neonates, particularly in preterm infants. The interleukin (IL) 23/IL17 axis has been shown to play an important role in the gastrointestinal inflammation. However, the association of gene polymorphisms in the IL23/IL17 axis and the development of NEC remains unknown. In this study, we aimed to explore a possible genetic role of IL23R and IL17 in the development of NEC. We identified single nucleotide polymorphisms (SNPs) in IL23R (rs10889677), IL17A (rs2275913), and IL17F (rs763780) by polymerase chain reaction and Sanger sequencing. A total of 102 NEC patients (stage II, n = 75; and stage III, n = 27) and 120 control subjects were recruited for the study. All of the participants were premature (gestational age < 37 weeks). Our results revealed that the combination of the IL17F rs763780 (TC + CC) genotype and the C allele both significantly increased the risk of NEC [odds ratio (OR) 1.89, 95% confidence interval (CI) 1.04-3.43, P = 0.035; OR 1.82, 95% CI 1.06-3.13, P = 0.028, respectively]. Furthermore, the rs763780 (TC + CC) genotype was associated with increased severity of NEC and the incidence of NEC-related perforation [OR 2.80, 95% CI 1.10-7.12, P = 0.031; OR 3.86, 95% CI 1.10-13.53, P = 0.035, respectively]. However, IL23R rs10889677 and IL17A rs2275913 were not associated with the susceptibility to NEC. In conclusion, our data suggest that a variant of IL17F (rs763780) may contribute to the development of NEC.
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Affiliation(s)
- Jiayi Tian
- Department of Neonatology, The First Hospital of Jilin University, Changchun, China.,Department of Central Laboratory, The First Hospital of Jilin University, Changchun, China
| | - Yanjun Liu
- Department of Neonatology, The First Hospital of Jilin University, Changchun, China.,Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University of Medicine and Sciences, University of California Los Angeles (UCLA) School of Medicine, Los Angeles, CA, USA
| | - Yanfang Jiang
- Department of Central Laboratory, The First Hospital of Jilin University, Changchun, China
| | - Haohan Zhou
- Department of Central Laboratory, The First Hospital of Jilin University, Changchun, China.,Department of Orthopedics Surgery, The Second Hospital of Jilin University, Changchun, China
| | - Tong Zhu
- Department of Neonatology, The First Hospital of Jilin University, Changchun, China
| | - Xiaoqi Zhao
- Department of Neonatology, The Second Hospital of Jilin University, Changchun, China
| | - Liping Peng
- Department of Central Laboratory, The First Hospital of Jilin University, Changchun, China. .,Department of Respirology, The First Hospital of Jilin University, Changchun, China.
| | - Chaoying Yan
- Department of Neonatology, The First Hospital of Jilin University, Changchun, China.
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24
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Eskandari-Nasab E, Moghadampour M, Tahmasebi A. Meta-Analysis of Risk Association Between Interleukin-17A and F Gene Polymorphisms and Inflammatory Diseases. J Interferon Cytokine Res 2017; 37:165-174. [PMID: 28186427 DOI: 10.1089/jir.2016.0088] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
This meta-analysis examined the relationship between IL-17A (rs2275913) and IL17F (rs763780 T/C) gene polymorphisms and the risk of inflammatory diseases, including periodontitis, rheumatoid arthritis (RA), and inflammatory bowel disease. PubMed, MEDLINE, EMBASE, Web of Science, and Elsevier Science Direct were searched, and odds ratios (ORs) with 95% confidence interval (CI) were calculated to estimate the strength of the association. A total of 25 studies comprising 7,474 cases and 10,628 controls were included. Significant associations were found between inflammatory diseases and IL-17A rs2275913 A versus G allele (OR = 1.197, P = 0.033) and the GA versus GG genotype in the codominant model (OR = 1.406, P = 0.036). Our findings suggested that individuals who carry the rs2275913 A allele or GA genotype have a 20% or 41%-increased risk of inflammatory diseases compared with subjects with the G allele or GG genotype, respectively. With respect to IL-17F rs763780, the C versus T allele (OR = 1.94; P = 0.040), the TC versus TT (OR = 1.39; P = 0.041), the CC versus TT (OR = 2.71; P = 0.003), as well as the TC + CC versus TT genotype (OR = 1.83; P = 0.032) were risk factors for RA. In summary, our pooled analysis indicated that the IL-17A (rs2275913) and IL17F (rs763780 T/C) increased the RA risk.
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Affiliation(s)
- Ebrahim Eskandari-Nasab
- 1 Genetic of Non-Communicable Disease Research Center, Zahedan University of Medical Sciences , Zahedan, Iran .,2 Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences , Zahedan, Iran
| | - Mehdi Moghadampour
- 3 Department of Microbiology, School of Medicine, Isfahan University of Medical Sciences , Isfahan, Iran
| | - Arezoo Tahmasebi
- 4 Department of Statistics, School of Science, Amir Kabir University of Technology , Tehran, Iran
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25
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Zhou F, Qiu LX, Cheng L, Wang MY, Li J, Sun MH, Yang YJ, Wang JC, Jin L, Wang YN, Wei QY. Associations of genotypes and haplotypes of IL-17 with risk of gastric cancer in an eastern Chinese population. Oncotarget 2016; 7:82384-82395. [PMID: 27577072 PMCID: PMC5347698 DOI: 10.18632/oncotarget.11616] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2016] [Accepted: 07/28/2016] [Indexed: 12/30/2022] Open
Abstract
Interleukin-17 plays a crucial role in inflammation-related carcinogenesis. We hypothesize that genetic variants in IL-17 are associated with gastric cancer (GCa) risk, and we genotyped five potentially functional single nucleotide polymorphisms (SNPs) (rs1974226 G > A, rs2275913 A > G, rs3819024 A > G, rs4711998 A > G, and rs8193036 C > T) of IL-17 in 1121 GCa patients and 1216 cancer-free controls in an eastern Chinese population. Logistic regression analysis was used to calculate odds ratios (OR) and 95% confidence intervals (CI). Meta-analysis and genotype-mRNA expression correlation were performed to further validate positive associations. We found that an increased GCa risk was independently associated with rs1974226 (adjusted OR = 2.60, 95% CI = 1.27-5.32 for AA vs. GG + GA) and rs2275913 (adjusted OR = 1.33, 95% CI = 1.03-1.72 for GA + AA vs. GG), while a decreased GCa risk was independently associated with rs3819024 (adjusted OR = 0.72, 95% CI = 0.54-0.96 for GG vs. AA + AG). Additional meta-analyses confirmed the observed risk association with rs2275913. We also found that two IL-17 haplotypes (G-G-G-A-C) and (A-G-G-A-C) (in the order of rs1974226, rs2275913, rs3819024, rs4711998 and rs8193036) were associated with a reduced GCa risk (adjusted OR = 0.64, 95% CI = 0.46-0.89 and adjusted OR = 0.38, 95% CI = 0.17-0.81, respectively). However, the expression Quantitative Trait Locus (eQTL) analysis for the genotype-phenotype correlation did not find mRNA expression changes associated with either the genotypes. In conclusions, genetic variants of IL-17 are likely to be associated with risk of GCa, and additional larger studies with functional validation are needed to explore the molecular mechanisms underlying the observed associations.
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Affiliation(s)
- Fei Zhou
- Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Department of Oncology, Shanghai Jiaotong University Affiliated Shanghai First People's Hospital, Shanghai, China
| | - Li-Xin Qiu
- Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Lei Cheng
- Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Meng-Yun Wang
- Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Jin Li
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Meng-Hong Sun
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Ya-Jun Yang
- Ministry of Education Key Laboratory of Contemporary Anthropology, State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China
- Fudan-Taizhou Institute of Health Sciences, Taizhou, Jiangsu, China
| | - Jiu-Cun Wang
- Ministry of Education Key Laboratory of Contemporary Anthropology, State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China
- Fudan-Taizhou Institute of Health Sciences, Taizhou, Jiangsu, China
| | - Li Jin
- Ministry of Education Key Laboratory of Contemporary Anthropology, State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China
- Fudan-Taizhou Institute of Health Sciences, Taizhou, Jiangsu, China
| | - Ya-Nong Wang
- Department of Gastric Cancer and Soft Tissue Sarcoma Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Qing-Yi Wei
- Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Fudan University Shanghai Cancer Center, Shanghai, China
- Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA
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26
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Kim SY, Hur MS, Choi BG, Kim MJ, Lee YW, Choe YB, Ahn KJ. A preliminary study of new single polymorphisms in the T helper type 17 pathway for psoriasis in the Korean population. Clin Exp Immunol 2016; 187:251-258. [PMID: 27774581 DOI: 10.1111/cei.12888] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/18/2016] [Indexed: 12/21/2022] Open
Abstract
Psoriasis is a polygenic and multi-factorial disease showing ethnic differences in terms of its severity and frequency. Therapies targeting interleukin (IL)-17A, IL-17 receptor (IL-17R) and Janus kinases (JAKs) are in clinical development for the treatment of psoriasis, and their success suggests the essential role of these molecules in psoriasis. To investigate the genetic susceptibility in T helper type 17 (Th17) cell signal transduction pathways for promoting psoriasis, we performed candidate gene and linkage disequilibrium analysis. In 208 patients and 266 normal controls, we analysed 31 single nucleotide polymorphisms in 12 genes (CAMP, IL17A, IL17F, IL17RA, IL22, JAK1, JAK2, JAK3, STAT3, TLR7, TLR9 and TYK2; abbreviations: CAMP, human cathelicidin antimicrobial peptide; STAT-3, signal transducer and activator of transcription 3; TLR, Toll-like receptor; TYK2, tyrosine kinase 2). Patients with psoriasis showed a strong association for IL17F rs763780 [odds ratio (OR) = 3·27, P = 0·04], which results in a histidine-to-arginine substitution, and JAK2 rs2274471 (OR = 2·66, P = 0·02). In addition, JAK2 rs7849191 showed a protective pattern, met the significance threshold (OR = 0·77, P = 0·05) and showed a tendency for an inverse association with the frequency of early-onset psoriasis under age 40 years (P = 0·07). In haplotype analysis, JAK1 rs310241A/rs2780889T showed a protective effect (OR = 0·73, P = 0·03) in psoriasis. In conclusion, we report two new psoriasis-susceptibility loci, in IL17F and JAK2, as well as a newly identified late-onset associated protective JAK2 locus and a protective JAK1 haplotype in the Korean population.
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Affiliation(s)
- S Y Kim
- Department of Dermatology, Konkuk University, School of Medicine, Seoul, Korea
| | - M S Hur
- Department of Dermatology, Konkuk University, School of Medicine, Seoul, Korea
| | - B G Choi
- Department of Dermatology, Konkuk University, School of Medicine, Seoul, Korea
| | - M J Kim
- Department of Dermatology, Konkuk University, School of Medicine, Seoul, Korea
| | - Y W Lee
- Department of Dermatology, Konkuk University, School of Medicine, Seoul, Korea
| | - Y B Choe
- Department of Dermatology, Konkuk University, School of Medicine, Seoul, Korea
| | - K J Ahn
- Department of Dermatology, Konkuk University, School of Medicine, Seoul, Korea
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27
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Wang J, Liu Y, Xie L, Li S, Qin X. Association of IL-17A and IL-17F gene polymorphisms with chronic hepatitis B and hepatitis B virus-related liver cirrhosis in a Chinese population: A case-control study. Clin Res Hepatol Gastroenterol 2016; 40:288-296. [PMID: 26546176 DOI: 10.1016/j.clinre.2015.10.004] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2015] [Revised: 09/28/2015] [Accepted: 10/06/2015] [Indexed: 02/04/2023]
Abstract
BACKGROUND Interleukin (IL)-17 has been shown to play an important role in tissue inflammation and in the pathogenesis of immune-related liver damage. Genetic variations in IL-17 gene may be associated with the development of hepatitis B virus (HBV) infection. However, literature is scanty regarding their association. METHODS We conducted a case-control study including 433 subjects (171 healthy controls, 130 patients with chronic hepatitis B [CHB]; and 132 patients with HBV-related liver cirrhosis [HBV-LC] to assess the association between IL-17A rs4711998, IL-17A rs2275913 and IL-17F rs763780 polymorphisms and risk of CHB and HBV-LC. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing. RESULTS Our results revealed a statistically significant association between IL-17A rs4711998 G allele and increased risk of HBV-LC risk (OR=1.541, 95% CI 1.057-2.246, P=0.025). Subjects carrying the IL-17A rs4711998 AG genotype were 1.75 times more likely to develop HBV-LC (OR=1.757, 95% CI 1.096-2.817, P=0.026). Stratification analysis indicated that IL-17A rs4711998 G allele and AG genotype enhanced the risk of HBV-LC development among men and older age (≥50years) subject groups. In addition, we found that GCT haplotype also might be a risk factor for HBV-LC (OR=2.448, 95% CI 1.137-5.271, P=0.019). Furthermore, no significant association between IL-17A rs2275913 and IL-17F rs763780 polymorphisms and CHB, HBV-LC risk was observed (P>0.05). CONCLUSION Our data provide the first evidence that the IL-17A rs4711998 genetic variant may contribute to HBV-LC susceptibility in a Chinese population.
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Affiliation(s)
- Jian Wang
- Department of Clinical Laboratory, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Yanqiong Liu
- Department of Clinical Laboratory, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Li Xie
- Department of Clinical Laboratory, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Shan Li
- Department of Clinical Laboratory, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
| | - Xue Qin
- Department of Clinical Laboratory, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
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28
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Xu H, Pan Y, Li W, Fu H, Zhang J, Shen H, Han X. Association between IL17A and IL17F polymorphisms and risk of Henoch–Schonlein purpura in Chinese children. Rheumatol Int 2016; 36:829-35. [DOI: 10.1007/s00296-016-3465-8] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2015] [Accepted: 03/12/2016] [Indexed: 12/19/2022]
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29
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Li N, Wang XM, Jiang LJ, Zhang M, Li N, Wei ZZ, Zheng N, Zhao YJ. Effects of endoplasmic reticulum stress on the expression of inflammatory cytokines in patients with ulcerative colitis. World J Gastroenterol 2016; 22:2357-2365. [PMID: 26900298 PMCID: PMC4735010 DOI: 10.3748/wjg.v22.i7.2357] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2015] [Revised: 09/05/2015] [Accepted: 11/30/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To explore the changes of X-box binding protein 1 splicing (XBP1s) and inflammatory cytokine expression in patients with ulcerative colitis (UC) in response to endoplasmic reticulum stress (ERS).
METHODS: Reverse transcription polymerase chain reaction and quantitative polymerase chain reaction were performed to detect the forms of XBP1s and the expression of interleukin (IL)-2, interferon (IFN)-γ, and IL-17α. Differences between patients with UC and normal subjects were then determined.
RESULTS: Mononuclear cells of the peripheral blood of normal subjects and UC patients with were stimulated with no drugs (control), phytohemagglutinin (PHA), thapsigargin (TG), or both PHA and TG. XBP1s in patients with UC exhibited splicing, which was greater with co-stimulation than single stimulation. Co-stimulation increased the expression level of IL-2, IFN-γ, and IL-17α.
CONCLUSION: The T lymphocytes of both normal subjects and patients with UC responded to ERS by activating the XBP1s-mediated signalling pathway, upregulating the expression of inflammatory cytokines, and increasing the occurrence of inflammation. The mononuclear cells in the peripheral blood of patients with UC were more sensitive to ERS than those in the peripheral blood of normal subjects.
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30
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Jiang YX, Li GM, Yi D, Yu PW. A meta-analysis: The association between interleukin-17 pathway gene polymorphism and gastrointestinal diseases. Gene 2015; 572:243-51. [DOI: 10.1016/j.gene.2015.07.018] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2015] [Revised: 06/18/2015] [Accepted: 07/07/2015] [Indexed: 02/07/2023]
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Prieto-Pérez R, Solano-López G, Cabaleiro T, Román M, Ochoa D, Talegón M, Baniandrés O, López Estebaranz JL, de la Cueva P, Daudén E, Abad-Santos F. The polymorphism rs763780 in the IL-17F gene is associated with response to biological drugs in patients with psoriasis. Pharmacogenomics 2015; 16:1723-31. [DOI: 10.2217/pgs.15.107] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Psoriasis improves when IL-17 is blocked. Anti-TNF drugs reduce the IL-17 signaling pathway, and anti-IL-17 drugs are being developed to treat moderate-to-severe psoriasis. We analyzed three SNPs in IL-17A (rs2275913 and rs10484879) and IL-17F (rs763780) to look for an association with psoriasis and/or with response to anti-TNF drugs or ustekinumab. We included 197 healthy controls and 194 patients with moderate-to-severe psoriasis. The results of the univariate analysis showed an association between rs10484879 and psoriasis, although this relationship disappeared after adjustment for HLA-C (rs12191877). We also found an association between rs763780 (IL-17F) and response to ustekinumab (n = 70) and infliximab (n = 37) at 3 and 6 months and an association between rs763780 and the response to adalimumab at 6 months (n = 67).
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Affiliation(s)
- Rocío Prieto-Pérez
- Clinical Pharmacology Service, Hospital Universitario de la Princesa, Instituto Teófilo Hernando, University Autónoma de Madrid (UAM), Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain
| | - Guillermo Solano-López
- Dermatology Service, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain
| | - Teresa Cabaleiro
- Clinical Pharmacology Service, Hospital Universitario de la Princesa, Instituto Teófilo Hernando, University Autónoma de Madrid (UAM), Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Manuel Román
- Clinical Pharmacology Service, Hospital Universitario de la Princesa, Instituto Teófilo Hernando, University Autónoma de Madrid (UAM), Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain
| | - Dolores Ochoa
- Clinical Pharmacology Service, Hospital Universitario de la Princesa, Instituto Teófilo Hernando, University Autónoma de Madrid (UAM), Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain
| | - María Talegón
- Clinical Pharmacology Service, Hospital Universitario de la Princesa, Instituto Teófilo Hernando, University Autónoma de Madrid (UAM), Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain
| | - Ofelia Baniandrés
- Dermatology Service, Hospital Universitario Gregorio Marañón, 28007 Madrid, Spain
| | | | - Pablo de la Cueva
- Dermatology Service, Hospital Universitario Infanta Leonor, 28031 Madrid, Spain
| | - Esteban Daudén
- Dermatology Service, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain
| | - Francisco Abad-Santos
- Clinical Pharmacology Service, Hospital Universitario de la Princesa, Instituto Teófilo Hernando, University Autónoma de Madrid (UAM), Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain
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Erkol İnal E, Görükmez O, Dündar Ü, Görükmez Ö, Yener M, Özemri Sağ Ş, Yakut T. The Influence of Polymorphisms of Interleukin-17A and -17F Genes on Susceptibility and Activity of Rheumatoid Arthritis. Genet Test Mol Biomarkers 2015; 19:461-4. [DOI: 10.1089/gtmb.2015.0064] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Affiliation(s)
- Esra Erkol İnal
- Department of Physical Medicine and Rehabilitation, Faculty of Medicine, Süleyman Demirel University, Isparta, Turkey
| | - Orhan Görükmez
- Department of Medical Genetics, Bursa Şevket Yılmaz Education and Research Hospital, Bursa, Turkey
| | - Ümit Dündar
- Department of Physical Medicine and Rehabilitation, Faculty of Medicine, Afyon Kocatepe University, Afyon, Turkey
| | - Özlem Görükmez
- Department of Medical Genetics, Faculty of Medicine, Uludağ University, Bursa, Turkey
| | - Mahmut Yener
- Department of Physical Medicine and Rehabilitation, Faculty of Medicine, Süleyman Demirel University, Isparta, Turkey
| | - Şebnem Özemri Sağ
- Department of Medical Genetics, Faculty of Medicine, Uludağ University, Bursa, Turkey
| | - Tahsin Yakut
- Department of Medical Genetics, Faculty of Medicine, Uludağ University, Bursa, Turkey
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Omrane I, Medimegh I, Baroudi O, Ayari H, Bedhiafi W, Stambouli N, Ferchichi M, Kourda N, Bignon YJ, Uhrhammer N, Mezlini A, Bougatef K, Benammar-Elgaaied A. Involvement of IL17A, IL17F and IL23R Polymorphisms in Colorectal Cancer Therapy. PLoS One 2015; 10:e0128911. [PMID: 26083022 PMCID: PMC4470506 DOI: 10.1371/journal.pone.0128911] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2014] [Accepted: 05/03/2015] [Indexed: 12/19/2022] Open
Abstract
IL23/IL17 pathway plays an important role in the development of inflammatory bowel diseases (IBD). In general, the genes encoding the cytokines are genetically polymorphic and polymorphisms in genes IL23R and IL17 have been proved to be associated with its susceptibility to inflammatory diseases as well as cancer including colorectal cancer. Moreover, it has been shown that these interleukins are involved in anti-tumor or pro-tumor effects of various cancers. Previously, we showed that there is a significant association between IL17A, IL17F and IL23R polymorphisms as well as the occurrence of colorectal cancer and the clinical features of the disease. The purpose of the present work is to investigate an association between IL17A, IL17F and IL23R polymorphisms in 102 Tunisian patients with colorectal cancer treatment. The association was analyzed by statistical tools. We found that patients with mutated genotypes of IL17A G197A SNP could be a risk factor for the inefficiency of chemotherapy and radiotherapy. Unlike IL17F variant, patients with wild type genotypes require surgery and adjuvant chemotherapy. On the one hand, we found no evidence that supports a significant association between IL23R polymorphism and the combined genotypes of these three genes and the colorectal cancer treatment. On the other hand, we showed that there is an important interaction between IL17A/IL17F polymorphisms and the stage of the disease as well as its treatment. Finally, patients with IL17F wild type genotype highlighted that there is a valid longer OS without all treatments and with radiotherapy and a neoadjuvant chemotherapy. In contrast, we observed that there are no relationships between IL17A, IL23R and the survival of these patients neither with nor without the treatment. Our results suggest that polymorphisms in IL17A and IL17F genes may be a predictive source of colorectal cancer therapy type. Therefore, IL17F may serve as an independent prognostic factor for overall survival in patients with colorectal cancer.
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Affiliation(s)
- Inés Omrane
- Laboratory of Genetics, Immunology and Human Pathology, Faculty of Sciences of Tunis, University Tunis El Manar, Tunis, Tunisia
- * E-mail:
| | - Imen Medimegh
- Laboratory of Genetics, Immunology and Human Pathology, Faculty of Sciences of Tunis, University Tunis El Manar, Tunis, Tunisia
| | - Olfa Baroudi
- Laboratory of Genetics, Immunology and Human Pathology, Faculty of Sciences of Tunis, University Tunis El Manar, Tunis, Tunisia
| | - Hager Ayari
- Laboratory of Genetics, Immunology and Human Pathology, Faculty of Sciences of Tunis, University Tunis El Manar, Tunis, Tunisia
| | - Walid Bedhiafi
- Laboratory of Genetics, Immunology and Human Pathology, Faculty of Sciences of Tunis, University Tunis El Manar, Tunis, Tunisia
| | - Nejla Stambouli
- Laboratory of Genetics, Immunology and Human Pathology, Faculty of Sciences of Tunis, University Tunis El Manar, Tunis, Tunisia
| | - Marwa Ferchichi
- Laboratory of Genetics, Immunology and Human Pathology, Faculty of Sciences of Tunis, University Tunis El Manar, Tunis, Tunisia
| | - Nadia Kourda
- Laboratory of Anatomy and Cytopathology of the Charles Nicolle Hospital, Tunis, Tunisia
| | - Yves-Jean Bignon
- Laboratory of Diagnostic and Molecular Genetics, Centre Jean Perrin, Clermont Ferrand, France
| | - Nancy Uhrhammer
- Laboratory of Diagnostic and Molecular Genetics, Centre Jean Perrin, Clermont Ferrand, France
| | - Amel Mezlini
- Medical Oncology Department of the Institute Salah Azaiez, Tunis, Tunisia
| | - Karim Bougatef
- Laboratory of Genetics, Immunology and Human Pathology, Faculty of Sciences of Tunis, University Tunis El Manar, Tunis, Tunisia
| | - Amel Benammar-Elgaaied
- Laboratory of Genetics, Immunology and Human Pathology, Faculty of Sciences of Tunis, University Tunis El Manar, Tunis, Tunisia
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Alagarasu K, Bachal RV, Tillu H, Mulay AP, Kakade MB, Shah PS, Cecilia D. Association of combinations of interleukin-10 and pro-inflammatory cytokine gene polymorphisms with dengue hemorrhagic fever. Cytokine 2015; 74:130-6. [PMID: 25890879 DOI: 10.1016/j.cyto.2015.03.021] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2014] [Revised: 03/11/2015] [Accepted: 03/31/2015] [Indexed: 12/26/2022]
Abstract
Pro-inflammatory and anti-inflammatory cytokines have been shown to play an important role in dengue disease pathogenesis. In the present study, to find out whether single nucleotide polymorphisms (SNPs) in the pro-inflammatory and anti-inflammatory cytokine genes are associated with dengue disease severity, SNPs in TNF, IFNG, IL1B, IL8, IL0, IL17A and IL17F genes were investigated using polymerase chain reaction based methods in 132 dengue (DEN) cases [87 dengue fever (DF), 45 dengue hemorrhagic fever (DHF) cases] and 108 apparently healthy controls (HC) from Pune, Maharashtra, western India. Under recessive genetic model (C/C vs. T/T+T/C), the TNF rs1799964 C/C genotype was significantly associated with DEN [P=0.014, OR with 95% CI 3.07 (1.18-7.98)]. Frequency of T/C genotype of IL17F rs763780 was significantly lower in DEN group as compared to HC [P=0.033, OR with 95% CI 0.43 (0.19-0.95)]. Under overdominant genetic model (A/T vs. A/A+T/T), IL8 rs4973 A/T genotype was negatively associated with DHF compared to HCs [p=0.029, OR with 95% CI 0.43 (0.20-0.93)]. Under overdominant genetic model, A/G genotype of IL10 rs1800871 was significantly negatively associated with DHF compared to DF cases [p=0.014, OR with 95% CI 0.35 (0.15-0.84)]. Significantly higher frequency of the combined genotype IL10 A/A-IFNG A/T and lower frequency of the combined genotypes IL10 A/G-IL1B A/A, IL10 A/G-IL8 A/T and IL10 A/G-IL17F T/T were observed in DHF cases compared to DF. The results suggest that heterozygous genotypes of IL8 rs4973 and IL10 rs1800871 are associated with reduced risk of DHF. Combinations of IL10 rs1800871 and pro-inflammatory cytokine genotypes influence the risk of DHF.
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Affiliation(s)
- K Alagarasu
- Dengue Group, National Institute of Virology, 20 A, Dr Ambedkar Road, Pune 411001, Maharashtra, India.
| | - R V Bachal
- Dengue Group, National Institute of Virology, 20 A, Dr Ambedkar Road, Pune 411001, Maharashtra, India
| | - H Tillu
- Dengue Group, National Institute of Virology, 20 A, Dr Ambedkar Road, Pune 411001, Maharashtra, India
| | - A P Mulay
- Dengue Group, National Institute of Virology, 20 A, Dr Ambedkar Road, Pune 411001, Maharashtra, India
| | - M B Kakade
- Dengue Group, National Institute of Virology, 20 A, Dr Ambedkar Road, Pune 411001, Maharashtra, India
| | - P S Shah
- Dengue Group, National Institute of Virology, 20 A, Dr Ambedkar Road, Pune 411001, Maharashtra, India
| | - D Cecilia
- Dengue Group, National Institute of Virology, 20 A, Dr Ambedkar Road, Pune 411001, Maharashtra, India
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Vargas-Alarcón G, Angeles-Martínez J, Villarreal-Molina T, Alvarez-León E, Posadas-Sánchez R, Cardoso-Saldaña G, Ramírez-Bello J, Pérez-Hernández N, Juárez-Rojas JG, Rodríguez-Pérez JM, Fragoso JM, Posadas-Romero C. Interleukin-17A gene haplotypes are associated with risk of premature coronary artery disease in Mexican patients from the Genetics of Atherosclerotic Disease (GEA) study. PLoS One 2015; 10:e0114943. [PMID: 25615631 PMCID: PMC4304820 DOI: 10.1371/journal.pone.0114943] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2014] [Accepted: 11/11/2014] [Indexed: 01/17/2023] Open
Abstract
Aim The role of interleukin 17A (IL-17A) in the inflammatory process has caused interest in the potential significance of IL-17A as a biomarker for coronary artery disease (CAD). The aim of the present study was to evaluate the role of IL-17A gene polymorphisms as susceptibility markers for CAD in the Mexican population. Methods Four IL-17A gene polymorphisms (rs8193036, rs3819024, rs2275913 and rs8193037) were genotyped by 5’ exonuclease TaqMan assays in a group of 900 patients with premature CAD and 667 healthy controls (with negative calcium score by computed tomography), seeking associations with CAD and other metabolic and cardiovascular risk factors using logistic regression analyses. Results No single IL-17A polymorphism was associated with premature CAD, however two haplotypes (CAGG and TAGA) were significantly associated with increased risk of premature CAD (OR = 1.35, 95% CI: 1.00–1.84, P = 0.018 and OR = 2.09, 95% CI: 1.16–3.76, P = 0.003, respectively). Moreover, rs3819024 was associated with increased levels of visceral abdominal fat (P = 0.002) and rs8193036 was significantly associated with risk of central obesity (P = 0.020), hypertriglyceridemia (P = 0.027), and metabolic syndrome (P = 0.027) in the premature CAD group, under dominant models adjusted by age, gender, BMI, smoking history, alcohol consumption, and treatment. Conclusion The results suggest that IL-17A haplotypes are involved in the risk of developing premature CAD and some IL-17A polymorphisms are associated with cardiovascular risk factors in Mexican individuals with premature CAD.
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Affiliation(s)
- Gilberto Vargas-Alarcón
- Departments of Molecular Biology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico
| | - Javier Angeles-Martínez
- Departments of Molecular Biology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico
| | - Teresa Villarreal-Molina
- Cardiovascular Genomics Laboratory, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico
| | - Edith Alvarez-León
- Departments of Molecular Biology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico
| | | | | | - Julian Ramírez-Bello
- Laboratory of Genomic Medicine, Unit of Research, Hospital Juárez de Mexico, Mexico City, Mexico
| | - Nonanzit Pérez-Hernández
- Departments of Molecular Biology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico
| | | | | | - José Manuel Fragoso
- Departments of Molecular Biology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico
| | - Carlos Posadas-Romero
- Department of Endocrinology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico
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Cheng S, Shao Z, Liu X, Guo L, Zhang X, Na Q, Chen X, Ma Y, Zheng J, Song B, Liu J. Interleukin 17A Polymorphism Elevates Gene Expression and Is Associated with Increased Risk of Nonsmall Cell Lung Cancer. DNA Cell Biol 2015; 34:63-8. [PMID: 25289477 DOI: 10.1089/dna.2014.2628] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Affiliation(s)
- Sensen Cheng
- School of Medicine and Life Sciences, University of Jinan, Shandong Academy of Medical Sciences, Jinan, China
| | - Zhulin Shao
- School of Medicine and Life Sciences, University of Jinan, Shandong Academy of Medical Sciences, Jinan, China
| | - Xiuchun Liu
- Department of Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Jinan, China
| | - Liangjun Guo
- Department of Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Jinan, China
| | - Xia Zhang
- Department of Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Jinan, China
| | - Qinyun Na
- Department of Surgery, Huadong Hospital, Shanxi, China
| | - Xiaofeng Chen
- Department of Surgery, Huadong Hospital, Shanxi, China
| | - Yuan Ma
- School of Medicine and Life Sciences, University of Jinan, Shandong Academy of Medical Sciences, Jinan, China
| | - Jinsong Zheng
- Department of Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Jinan, China
| | - Bao Song
- Department of Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Jinan, China
| | - Jie Liu
- Department of Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Jinan, China
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Li J, Tian H, Jiang HJ, Han B. Interleukin-17 SNPs and serum levels increase ulcerative colitis risk: A meta-analysis. World J Gastroenterol 2014; 20:15899-15909. [PMID: 25400476 PMCID: PMC4229557 DOI: 10.3748/wjg.v20.i42.15899] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2013] [Revised: 04/05/2014] [Accepted: 06/13/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the associations of interleukin-17 (IL-17) genetic polymorphisms and serum levels with ulcerative colitis (UC) risk.
METHODS: Relevant articles were identified through a search of the following electronic databases, excluding language restriction: (1) the Cochrane Library Database (Issue 12, 2013); (2) Web of Science (1945-2013); (3) PubMed (1966-2013); (4) CINAHL (1982-2013); (5) EMBASE (1980-2013); and (6) the Chinese Biomedical Database (1982-2013). Meta-analysis was conducted using STATA 12.0 software. Crude odds ratios and standardized mean differences (SMDs) with corresponding 95% confidence intervals (CIs) were calculated. All of the included studies met all of the following five criteria: (1) the study design must be a clinical cohort or a case-control study; (2) the study must relate to the relationship between IL-17A/F genetic polymorphisms or serum IL-17 levels and the risk of UC; (3) all patients must meet the diagnostic criteria for UC; (4) the study must provide sufficient information about single nucleotide polymorphism frequencies or serum IL-17 levels; and (5) the genotype distribution of healthy controls must conform to the Hardy-Weinberg equilibrium (HWE). The Newcastle-Ottawa Scale (NOS) criteria were used to assess the methodological quality of the studies. The NOS criteria included three aspects: (1) subject selection: 0-4; (2) comparability of subjects: 0-2; and (3) clinical outcome: 0-3. NOS scores ranged from 0 to 9, with a score ≥ 7 indicating good quality.
RESULTS: Of the initial 177 articles, only 16 case-control studies met all of the inclusion criteria. A total of 1614 UC patients and 2863 healthy controls were included in this study. Fourteen studies were performed on Asian populations, and two studies on Caucasian populations. Results of the meta-analysis revealed that IL-17A and IL-17F genetic polymorphisms potentially increased UC risk under both allele and dominant models (P < 0.001 for all). The results also showed that UC patients had higher serum IL-17 levels than healthy controls (SMD = 5.95, 95%CI: 4.25-7.65, P < 0.001). Furthermore, serum IL-17 levels significantly correlated with the severity of UC (moderate vs mild: SMD = 2.59, 95%CI: 0.03-5.16, P < 0.05; severe vs mild: SMD = 7.09, 95%CI: 3.96-10.23, P < 0.001; severe vs moderate: SMD = 5.84, 95%CI: 5.09-6.59, P < 0.001). The NOS score was ≥ 5 for all of the included studies. Based on the sensitivity analysis, no single study influenced the overall pooled estimates. Neither the Begger’s funnel plots nor Egger’s test displayed strong statistical evidence for publication bias (IL-17A/F genetic polymorphisms: t = -2.60, P = 0.019; serum IL-17 levels: t = -1.54, P = 0.141).
CONCLUSION: The findings strongly suggest that IL-17A/F genetic polymorphisms and serum IL-17 levels contribute to the development and progression of UC.
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Ren Z, Li M, Liu R, Wang Y, Gu H. Interleukin 17A rs3819024 A>G polymorphism is associated with an increased risk of gastric cardia adenocarcinoma in a Chinese population. Biomarkers 2014; 19:411-6. [PMID: 24893702 DOI: 10.3109/1354750x.2014.924158] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Gastric cardia adenocarcinoma (GCA) is one of the most common malignant tumors. In addition to environmental risk factors, genetic factors might play an important role in GCA carcinogenesis. To evaluate the association between polymorphisms in the interleukin 17A (IL17A) gene on the development of GCA, we conducted a hospital-based case-control study. A total of 243 GCA cases and 476 controls were recruited and their genotypes were determined using a custom-by-design 48-Plex SNPscan™ Kit. IL17A rs3819024 A > G polymorphism was found to be associated with the increased risk of GCA. When the IL17A rs3819024 AA homozygote genotype was used as the reference group, the AG genotype was associated with a significantly increased risk of GCA (AG versus AA: adjusted OR = 1.53, 95% CI = 1.05-2.23, p = 0.026). However, there was no significant association between five other SNPs and GCA. Stratified analyses indicated that a significantly increased risk of GCA associated with the IL17A rs3819024 A > G polymorphism was evident among male patients, patients who drank alcohol or those who never smoked. These findings indicated that functional polymorphism IL17A rs3819024 A > G might contribute to GCA susceptibility. Future larger studies with more rigorous study designs are required to confirm the current findings.
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Affiliation(s)
- Zhengbing Ren
- Department of Cardiothoracic Surgery, Affiliated People's Hospital of Jiangsu University , Zhenjiang , China
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39
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Omrane I, Marrakchi R, Baroudi O, Mezlini A, Ayari H, Medimegh I, Stambouli N, Kourda N, Bouzaienne H, Uhrhammer N, Bougatef K, Bignon YJJ, Benammar-Elgaaied A. Significant association between interleukin-17A polymorphism and colorectal cancer. Tumour Biol 2014; 35:6627-32. [PMID: 24699997 DOI: 10.1007/s13277-014-1890-4] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2014] [Accepted: 03/25/2014] [Indexed: 12/21/2022] Open
Abstract
Interleukin (IL) 17A is an inflammatory cytokine expressed by Th 17 cells and plays a role in tissue inflammation by inducing release of proinflammatory and neutrophil-mobilizing cytokines. We have investigated the association between colorectal cancer and polymorphisms of IL17A (rs2275913. G197A). The study was performed in 241 subjects (102 with colorectal cancer and 139 healthy controls). Genotypes were determined by fluorescent-based restriction fragment length polymorphism method. The association between the molecular features at the gene in relation to tumor and patient clinical characteristics was analyzed. There was a significant difference between the genotype frequencies of IL17A G197A of control subjects (GG 68.34 % and GA + AA 31.65 %) and patients with colorectal cancer (GG 47.05 % and GA + AA 52.94 %) (p = 0.001 with odds ratio (OR) 2.45 (1.43-4.11)). IL17A G197A polymorphism is particularly associated with colon cancer. Indeed, the IL17A GG genotype could be considered as a protective factor against colon cancer (p = 0.00001) with OR 3.77 (2.04-6.99). We have noted a significant association of IL17A G197A polymorphism not only with tumor localization (p = 0.003) but also with tumor differentiation (p = 0.0005) in CRC patients. We have also showed a significant association of G197A variant with an increased risk of advanced stage (p = 0.005). Our result suggests that the A allele of IL17A gene is involved in susceptibility to colorectal cancer and is associated with clinical features as tumor location, tumor differentiation, and TNM stage. IL17A polymorphism may serve as biomarker of disease location and progression.
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Affiliation(s)
- Inés Omrane
- Laboratory of Human Genetics Immunology and Pathology, Faculty of Sciences Tunis, University of Tunis El Manar, El Manar, Tunis, 209, Tunisia,
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