Min Liu1, Wenqian Zhu1, Jun Wang1, Jixiang Zhang1, Xufeng Guo1, Jing Wang1, Jia Song1, Weiguo Dong2. 1. Department of Gastroenterology, Renmin Hospital of Wuhan University, 430060 Wuhan, Hubei, PR China. 2. Department of Gastroenterology, Renmin Hospital of Wuhan University, 430060 Wuhan, Hubei, PR China. Electronic address: dwg@whu.edu.cn.
Abstract
OBJECTIVE: The interleukin-23 receptor (IL-23R) polymorphism has been implicated in susceptibility to ulcerative colitis (UC), but the results remain inconclusive. This study was designed to evaluate whether IL-23R polymorphisms were associated with UC susceptibility. METHODS: CNKI, WanFang Data, PubMed, MEDLINE, Web of Science, Google Scholar, EBSCO, CBM database and EMBASE were searched until 31 June 2014 for eligible studies on eight IL-23R polymorphisms: rs11209026, rs7517847, rs1209032, rs2201841, rs1343151, rs1088967, rs1495965 and rs1004819. Meta-analysis from all eligible case-control studies was performed to assess the purported associations. Meta-analysis was performed by using the RevMan 5.2 software and STATA package version 12.0. RESULTS: Sixteen studies with 5438 cases and 7380 controls were included. Overall, our analysis found that variant minor alleles for single nucleotide polymorphisms (SNPs) rs11209026 (Arg381Gln) (dominant model: GG+TG vs. TT, P=0.02, OR=0.71, 95%CI: 0.53-0.94); rs7517847 (recessive model: GG vs. TT, P=0.04, OR=0.80, 95%CI: 0.65-0.99) and rs11209032 [dominant model: GA+AA vs. GG (P=0.04, OR=1.31, 95% CI: 1.01-1.26); AA vs. GG: (P=0.04, OR=1.21, 95% CI: 1.01-1.45)] of IL-23R were associated with UC risk. In stratification analysis by ethnicity, we observed that the rs11209026 and rs7517847 polymorphism of IL-23R could protect against development of UC among Caucasian populations [rs11209026: dominant model (P=0.01, OR=0.69, 95%CI: 0.52-0.92); rs7517847: GG vs. TT (P=0.002, OR=0.69, 95%CI: 0.54-0.87); recessive model (P=0.004, OR=0.73, 95% CI: 0.59-0.90)]; the rs11209032 were associated with a greater risk for UC in Caucasian populations [dominant model (P=0.04, OR=1.13, 95%CI: 1.00-1.26)]; the rs1088967 were associated with a lower risk for UC among Asian populations [dominant model (P=0.04, OR=0.73, 95%CI: 0.54-0.99)]. Moreover, meta-analysis revealed no association between the four alleles of the rs2201841, rs1004819, rs1495965 and rs1343151 polymorphisms and the risk of developing UC in Caucasian and Asian populations. CONCLUSION: Our meta-analysis supports that two polymorphisms (rs11209026 and rs7517847) in the IL-23 gene may be considered to be protective factors against developing UC among Caucasian populations; while the rs11209032 polymorphisms may increase the risk of UC among Caucasian populations; furthermore, the rs1088967 polymorphisms in the IL-23 gene may be considered to be protective factors against developing UC among Asian populations. Further large case-control studies especially concerning ethnicity differences and genotype-phenotype interaction should be performed to clarify possible roles of IL-23R in UC.
OBJECTIVE: The interleukin-23 receptor (IL-23R) polymorphism has been implicated in susceptibility to ulcerative colitis (UC), but the results remain inconclusive. This study was designed to evaluate whether IL-23R polymorphisms were associated with UC susceptibility. METHODS: CNKI, WanFang Data, PubMed, MEDLINE, Web of Science, Google Scholar, EBSCO, CBM database and EMBASE were searched until 31 June 2014 for eligible studies on eight IL-23R polymorphisms: rs11209026, rs7517847, rs1209032, rs2201841, rs1343151, rs1088967, rs1495965 and rs1004819. Meta-analysis from all eligible case-control studies was performed to assess the purported associations. Meta-analysis was performed by using the RevMan 5.2 software and STATA package version 12.0. RESULTS: Sixteen studies with 5438 cases and 7380 controls were included. Overall, our analysis found that variant minor alleles for single nucleotide polymorphisms (SNPs) rs11209026 (Arg381Gln) (dominant model: GG+TG vs. TT, P=0.02, OR=0.71, 95%CI: 0.53-0.94); rs7517847 (recessive model: GG vs. TT, P=0.04, OR=0.80, 95%CI: 0.65-0.99) and rs11209032 [dominant model: GA+AA vs. GG (P=0.04, OR=1.31, 95% CI: 1.01-1.26); AA vs. GG: (P=0.04, OR=1.21, 95% CI: 1.01-1.45)] of IL-23R were associated with UC risk. In stratification analysis by ethnicity, we observed that the rs11209026 and rs7517847 polymorphism of IL-23R could protect against development of UC among Caucasian populations [rs11209026: dominant model (P=0.01, OR=0.69, 95%CI: 0.52-0.92); rs7517847: GG vs. TT (P=0.002, OR=0.69, 95%CI: 0.54-0.87); recessive model (P=0.004, OR=0.73, 95% CI: 0.59-0.90)]; the rs11209032 were associated with a greater risk for UC in Caucasian populations [dominant model (P=0.04, OR=1.13, 95%CI: 1.00-1.26)]; the rs1088967 were associated with a lower risk for UC among Asian populations [dominant model (P=0.04, OR=0.73, 95%CI: 0.54-0.99)]. Moreover, meta-analysis revealed no association between the four alleles of the rs2201841, rs1004819, rs1495965 and rs1343151 polymorphisms and the risk of developing UC in Caucasian and Asian populations. CONCLUSION: Our meta-analysis supports that two polymorphisms (rs11209026 and rs7517847) in the IL-23 gene may be considered to be protective factors against developing UC among Caucasian populations; while the rs11209032 polymorphisms may increase the risk of UC among Caucasian populations; furthermore, the rs1088967 polymorphisms in the IL-23 gene may be considered to be protective factors against developing UC among Asian populations. Further large case-control studies especially concerning ethnicity differences and genotype-phenotype interaction should be performed to clarify possible roles of IL-23R in UC.
Authors: Julajak Limsrivilai; Krishna Rao; Ryan W Stidham; Shail M Govani; Akbar K Waljee; Andrew Reinink; Laura Johnson; Emily Briggs; Peter D R Higgins Journal: Dig Dis Sci Date: 2018-04-12 Impact factor: 3.199