Skip to main content
Top
Published in: Clinical and Experimental Medicine 4/2013

01-11-2013 | Original Article

Influence of IL17A polymorphisms (rs2275913 and rs3748067) on the susceptibility to ulcerative colitis

Authors: Ranji Hayashi, Tomomitsu Tahara, Hisakazu Shiroeda, Takashi Saito, Masakatsu Nakamura, Mikihiro Tsutsumi, Tomoyuki Shibata, Tomiyasu Arisawa

Published in: Clinical and Experimental Medicine | Issue 4/2013

Login to get access

Abstract

Interleukin-17A plays a role in tissue inflammation by inducing release of proinflammatory and neutrophil-mobilizing cytokines. We investigated the association between ulcerative colitis (UC) and polymorphisms of IL17A, rs2275913 (−197 G > A), and rs3748067 (*1249 C > T). The study was performed in 475 healthy subjects (controls) and 202 with UC (UC cases), including 113 controls and 64 UC cases from previous study. We employed the multiplex PCR-SSCP method to detect gene polymorphisms. The minor allele frequency of rs2275913 was significantly higher but that of rs3748067 was significantly lower in UC cases than controls. The rs2275913 minor homozygote (AA) had an increased risk of the development of UC, whereas rs3748067 minor carrier (CT + TT) had decreased risks for the development of UC. When compared with LR group (rs2275913 GG + GA with rs3748067 CT + TT), HR group (rs2275913 AA with rs3748067 CC) had a more increased risk of the development of UC (OR, 3.38; p = 0.0007). The polymorphisms of IL17A were associated with the noncontinuous and pancolitis phenotypes of UC. Our results suggest that IL17A polymorphisms (both rs2275913 and rs3748067) influence the susceptibility to and pathophysiological features of UC, coordinately.
Literature
2.
go back to reference Chamaillard M, Philpott D, Girardin SE, Zouali H, Lesage S, Chareyre F et al (2003) Gene-environment interaction modulated by allelic heterogeneity in inflammatory diseases. Proc Natl Acad Sci USA 100:3455–3460PubMedCrossRef Chamaillard M, Philpott D, Girardin SE, Zouali H, Lesage S, Chareyre F et al (2003) Gene-environment interaction modulated by allelic heterogeneity in inflammatory diseases. Proc Natl Acad Sci USA 100:3455–3460PubMedCrossRef
3.
go back to reference Head KA, Jurenka JS (2003) Inflammatory bowel disease part I: ulcerative colitis-pathophysiology and conventional and alternative treatment options. Altern Med Rev 8:247–283PubMed Head KA, Jurenka JS (2003) Inflammatory bowel disease part I: ulcerative colitis-pathophysiology and conventional and alternative treatment options. Altern Med Rev 8:247–283PubMed
4.
go back to reference Lakatos PL, Fischer S, Lakatos L, Gal I, Papp J (2006) Current concept on the pathogenesis of infl ammatory boweldisease-crosstalk between genetic and microbial factors: pathogenic bacteria and altered bacterial sensing or changes in mucosal integrity take “toll”? World J Gastroenterol 12:1829–1841PubMed Lakatos PL, Fischer S, Lakatos L, Gal I, Papp J (2006) Current concept on the pathogenesis of infl ammatory boweldisease-crosstalk between genetic and microbial factors: pathogenic bacteria and altered bacterial sensing or changes in mucosal integrity take “toll”? World J Gastroenterol 12:1829–1841PubMed
5.
go back to reference Blumberg RS, Strober W (2001) Prospects for research in inflammatory bowel diseases. JAMA 285:643–647PubMedCrossRef Blumberg RS, Strober W (2001) Prospects for research in inflammatory bowel diseases. JAMA 285:643–647PubMedCrossRef
6.
go back to reference Newman B, Siminovitch KA (2005) Recent advances in the genetics of inflammatory bowel disease. Curr Opin Gastroenterol 21:401–407PubMed Newman B, Siminovitch KA (2005) Recent advances in the genetics of inflammatory bowel disease. Curr Opin Gastroenterol 21:401–407PubMed
7.
go back to reference Tanaka M, Kazuma K (2005) Ulcerative colitis: factors affecting difficulties of life and psychological well being of patients in remission. J Clin Nurs 14:65–73PubMedCrossRef Tanaka M, Kazuma K (2005) Ulcerative colitis: factors affecting difficulties of life and psychological well being of patients in remission. J Clin Nurs 14:65–73PubMedCrossRef
8.
go back to reference Wang F, Tahara T, Arisawa T, Shibata T, Nakamura M, Fujita H et al (2007) Genetic polymorphisms of CD14 and Toll-like receptor-2 (TLR2) in patients with ulcerative colitis. J Gastroenterol Hepatol 22:925–929PubMedCrossRef Wang F, Tahara T, Arisawa T, Shibata T, Nakamura M, Fujita H et al (2007) Genetic polymorphisms of CD14 and Toll-like receptor-2 (TLR2) in patients with ulcerative colitis. J Gastroenterol Hepatol 22:925–929PubMedCrossRef
9.
go back to reference Arisawa T, Tahara T, Shibata T, Nagasaka M, Nakamura M, Kamiya Y et al (2008) The influence of polymorphisms of interleukin-17A and interleukin-17F genes on the susceptibility to ulcerative colitis. J Clin Immunol 28:44–49PubMedCrossRef Arisawa T, Tahara T, Shibata T, Nagasaka M, Nakamura M, Kamiya Y et al (2008) The influence of polymorphisms of interleukin-17A and interleukin-17F genes on the susceptibility to ulcerative colitis. J Clin Immunol 28:44–49PubMedCrossRef
10.
go back to reference Shiroeda H, Tahara T, Nakamura M, Shibata T, Nomura T, Yamada H et al (2010) Association between functional promoter polymorphisms of macrophage migration inhibitory factor (MIF) gene and ulcerative colitis in Japan. Cytokine 51:173–177PubMedCrossRef Shiroeda H, Tahara T, Nakamura M, Shibata T, Nomura T, Yamada H et al (2010) Association between functional promoter polymorphisms of macrophage migration inhibitory factor (MIF) gene and ulcerative colitis in Japan. Cytokine 51:173–177PubMedCrossRef
11.
go back to reference Okubo M, Tahara T, Shibata T, Yamashita H, Nakamura M, Yoshioka D et al (2011) Association study of common genetic variants in pre-microRNAs in patients with ulcerative colitis. J Clin Immunol 31:69–73PubMedCrossRef Okubo M, Tahara T, Shibata T, Yamashita H, Nakamura M, Yoshioka D et al (2011) Association study of common genetic variants in pre-microRNAs in patients with ulcerative colitis. J Clin Immunol 31:69–73PubMedCrossRef
12.
go back to reference Rutitzky LI, Lopes da Rosa JR, Stadecker MJ (2005) Severe CD4 T cell-mediated immunopathology in murine schistosomiasis is dependent on IL-12p40 and correlates with high levels of IL-17. J Immunol 175:3920–3926PubMed Rutitzky LI, Lopes da Rosa JR, Stadecker MJ (2005) Severe CD4 T cell-mediated immunopathology in murine schistosomiasis is dependent on IL-12p40 and correlates with high levels of IL-17. J Immunol 175:3920–3926PubMed
13.
go back to reference Aggarwal S, Ghilardi N, Xie MH, de Sauvage FJ, Gurney AL (2003) Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17. J Biol Chem 278:1910–1914PubMedCrossRef Aggarwal S, Ghilardi N, Xie MH, de Sauvage FJ, Gurney AL (2003) Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17. J Biol Chem 278:1910–1914PubMedCrossRef
14.
15.
go back to reference Fujino S, Andoh A, Bamba S, Ogawa A, Hata K, Araki Y et al (2003) Increased expression of interleukin 17 in inflammatory bowel disease. Gut 52:65–70PubMedCrossRef Fujino S, Andoh A, Bamba S, Ogawa A, Hata K, Araki Y et al (2003) Increased expression of interleukin 17 in inflammatory bowel disease. Gut 52:65–70PubMedCrossRef
16.
go back to reference Nielsen OH, Kirman I, Rudiger N, Hendel J, Vainer B (2003) Upregulation of interleukin-12 and -17 in active inflammatory bowel disease. Scand J Gastroenterol 38:180–185PubMedCrossRef Nielsen OH, Kirman I, Rudiger N, Hendel J, Vainer B (2003) Upregulation of interleukin-12 and -17 in active inflammatory bowel disease. Scand J Gastroenterol 38:180–185PubMedCrossRef
17.
go back to reference Zhang Z, Hinrichs DJ, Lu H, Chen H, Zhong W, Kolls JK (2007) After interleukin-12p40, are interleukin-23 and interleukin-17 the next therapeutic targets for inflammatory bowel disease? Int Immunopharmacol 7:409–416PubMedCrossRef Zhang Z, Hinrichs DJ, Lu H, Chen H, Zhong W, Kolls JK (2007) After interleukin-12p40, are interleukin-23 and interleukin-17 the next therapeutic targets for inflammatory bowel disease? Int Immunopharmacol 7:409–416PubMedCrossRef
18.
go back to reference Shibata T, Tahara T, Hirata I, Arisawa T (2009) Genetic polymorphism of interleukin-17A and -17F genes in gastric carcinogenesis. Hum Immunol 70:547–551PubMedCrossRef Shibata T, Tahara T, Hirata I, Arisawa T (2009) Genetic polymorphism of interleukin-17A and -17F genes in gastric carcinogenesis. Hum Immunol 70:547–551PubMedCrossRef
19.
go back to reference Nordang GBN, Viken MK, Hollis-Moffatt JE, Merriman TR, Forre OT, Helgetveit K et al (2009) Association analysis of the interleukin 17A gene in Caucasian rheumatoid arthritis patients from Norway and New Zealand. Rheumatology 48:367–370PubMedCrossRef Nordang GBN, Viken MK, Hollis-Moffatt JE, Merriman TR, Forre OT, Helgetveit K et al (2009) Association analysis of the interleukin 17A gene in Caucasian rheumatoid arthritis patients from Norway and New Zealand. Rheumatology 48:367–370PubMedCrossRef
20.
go back to reference Wu X, Zeng Z, Chen B, Yu J, Xue L, Hao Y et al (2010) Association between polymorphisms in interleukin-17A and interleukin-17F genes and risks of gastric cancer. Int J Cancer 127:86–92PubMedCrossRef Wu X, Zeng Z, Chen B, Yu J, Xue L, Hao Y et al (2010) Association between polymorphisms in interleukin-17A and interleukin-17F genes and risks of gastric cancer. Int J Cancer 127:86–92PubMedCrossRef
21.
go back to reference Chen J, Deng Y, Zhao J, Luo Z, Peng W, Yang J et al (2010) The polymorphism of IL-17 G-152A was associated with childhood asthma and bacterial colonization of the hypopharynx in bronchiolitis. J Clin Immunol 30:539–545PubMedCrossRef Chen J, Deng Y, Zhao J, Luo Z, Peng W, Yang J et al (2010) The polymorphism of IL-17 G-152A was associated with childhood asthma and bacterial colonization of the hypopharynx in bronchiolitis. J Clin Immunol 30:539–545PubMedCrossRef
22.
go back to reference Mishra PJ, Bertino JR (2009) MicroRNA polymorphisms: the future of pharmacogenomics, molecular epidemiology and individualized medicine. Pharmacogenomics 10:399–416PubMedCrossRef Mishra PJ, Bertino JR (2009) MicroRNA polymorphisms: the future of pharmacogenomics, molecular epidemiology and individualized medicine. Pharmacogenomics 10:399–416PubMedCrossRef
24.
go back to reference Arisawa T, Tahara T, Shibata T, Nagasaka M, Nakamura M, Kamiya Y et al (2007) The relationship between Helicobacter Pylori infection and promoter polymorphism of the Nrf2 gene in chronic gastritis. Int J Mol Med 19:143–148PubMed Arisawa T, Tahara T, Shibata T, Nagasaka M, Nakamura M, Kamiya Y et al (2007) The relationship between Helicobacter Pylori infection and promoter polymorphism of the Nrf2 gene in chronic gastritis. Int J Mol Med 19:143–148PubMed
25.
go back to reference O’Connor W Jr, Kamanaka M, Booth CJ, Town T, Nakae S, Iwakura Y et al (2009) A protective function for interleukin 17A in T cell-mediated intestinal inflammation. Nat Immunol 10:603–609PubMedCrossRef O’Connor W Jr, Kamanaka M, Booth CJ, Town T, Nakae S, Iwakura Y et al (2009) A protective function for interleukin 17A in T cell-mediated intestinal inflammation. Nat Immunol 10:603–609PubMedCrossRef
26.
go back to reference Ouyang W, Kolls JK, Zheng Y (2008) The biological functions of T helper 17 cell effector cytokines in inflammation. Immunity 28:454–467PubMedCrossRef Ouyang W, Kolls JK, Zheng Y (2008) The biological functions of T helper 17 cell effector cytokines in inflammation. Immunity 28:454–467PubMedCrossRef
27.
go back to reference Sethupathy P, Collins FS (2008) MicroRNA target site polymorphisms and human disease. Trends Genet 24:489–497PubMedCrossRef Sethupathy P, Collins FS (2008) MicroRNA target site polymorphisms and human disease. Trends Genet 24:489–497PubMedCrossRef
28.
go back to reference Kertesz M, Iovino N, Unnerstall U, Gaul U, Segal E (2007) The role of site accessibility in microRNA target recognition. Nat Genet 39:1278–1284PubMedCrossRef Kertesz M, Iovino N, Unnerstall U, Gaul U, Segal E (2007) The role of site accessibility in microRNA target recognition. Nat Genet 39:1278–1284PubMedCrossRef
Metadata
Title
Influence of IL17A polymorphisms (rs2275913 and rs3748067) on the susceptibility to ulcerative colitis
Authors
Ranji Hayashi
Tomomitsu Tahara
Hisakazu Shiroeda
Takashi Saito
Masakatsu Nakamura
Mikihiro Tsutsumi
Tomoyuki Shibata
Tomiyasu Arisawa
Publication date
01-11-2013
Publisher
Springer Milan
Published in
Clinical and Experimental Medicine / Issue 4/2013
Print ISSN: 1591-8890
Electronic ISSN: 1591-9528
DOI
https://doi.org/10.1007/s10238-012-0206-5

Other articles of this Issue 4/2013

Clinical and Experimental Medicine 4/2013 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine