Abstract
ObjectivesSince a genome-wide association study revealed that Interleukin-23 receptor (IL-23R) gene is a candidate gene for Ulcerative Colitis (UC), many studies have investigated the association between the IL-23R polymorphisms and UC. However, the results were controversial. The aim of the study was to determine whether the IL-23R polymorphisms confer susceptibility to UC.MethodsA systematic literature search was carried out to identify all potentially relevant studies. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the strength of association.ResultsA total of 33 studies in 32 articles, including 10,527 UC cases and 15,142 healthy controls, were finally involved in the meta-analysis. Overall, a significant association was found between all UC cases and the rs11209026A allele (OR = 0.665, 95% CI = 0.604~0.733, P < 0.001). Similarly, meta-analyses of the rs7517847, rs1004819, rs10889677, rs2201841, rs11209032, rs1495965, rs1343151 and rs11465804 polymorphisms also indicated significant association with all UC (all P < 0.05). Stratification by ethnicity revealed that the rs11209026, rs7517847, rs10889677, rs2201841 andrs11465804 polymorphisms were associated with UC in the Caucasian group, but not in Asians, while the rs1004819 and rs11209032 polymorphisms were found to be related to UC for both Caucasian and Asian groups. However, subgroup analysis failed to unveil any association between the rs1495965 and rs1343151 polymorphisms and UC in Caucasians or Asians.ConclusionsThe meta-analysis suggests significant association between IL-23R polymorphisms and UC, especially in Caucasians.
Highlights
Ulcerative Colitis (UC) is a chronic relapsing and remitting intestinal inflammatory disorder that is confined to the mucosal and submucosal layers of rectum and colon, invading epithelial lining of the gut [1, 2]
A significant association was found between all UC cases and the rs11209026A allele (OR = 0.665, 95% confidence interval (CI) = 0.604~0.733, P < 0.001)
Stratification by ethnicity revealed that the rs11209026, rs7517847, rs10889677, rs2201841 andrs11465804 polymorphisms were associated with UC in the Caucasian group, but not in Asians, while the rs1004819 and rs11209032 polymorphisms were found to be related to UC for both Caucasian and Asian groups
Summary
Ulcerative Colitis (UC) is a chronic relapsing and remitting intestinal inflammatory disorder that is confined to the mucosal and submucosal layers of rectum and colon, invading epithelial lining of the gut [1, 2]. The etiology and pathogenesis of UC are still unclear, but the epidemiological data have suggested that genetic variation is a major risk factor for the evolution of UC [3, 4]. A genome-wide association study (GWAS) in north Indian identified three novel human leucocyte antigen (HLA)-independent UC risk loci from chromosome 6 [5]. A novel locus at 6q22.1 was found to be associated with UC in a south European population [6]. Approximately 100 UC susceptibility loci have identified via GWAS studies and immnochip data, and these loci are implicated in the pathphysiologic mechanisms of UC, including microbe recognition, lymphocyte activation, cytokine signaling and intestinal epithelial defense [4,5,6,7,8,9]. Genetic www.impactjournals.com/oncotarget studies provide clues on the immunopathogenesis for the disease, highlighting the role of immunity in the disease development of UC
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