Abstract
BackgroundMany studies have investigated the associations between the signal transducer and activator of transcription 3 (STAT3) in the susceptibility to ulcerative colitis (UC) and Crohn's disease (CD). However, the results remain inconsistent. This meta-analysis determined the risk of STAT3 rs744166 polymorphism-conferred UC and CD susceptibility.Materials and MethodsElectronic databases, including PubMed, EMBASE and the Cochrane Library, were searched for all eligible studies that evaluated the association between STAT3 rs744166 polymorphisms with UC and CD risk up to August 21, 2014. The pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using fixed- or random-effects models.ResultsTwelve studies containing 10298 patients with CD, 4244 patients with UC and 11191 controls were included in this meta-analysis. The results indicated that the STAT3 rs744166 polymorphism was associated with CD and UC susceptibility (CD: GA+AA vs. GG, OR = 1.20, 95%CI, 1.11–1.30, I 2 = 0%, P unadjusted<0.00001, P Bonferroni<0.00005, P FDR<0.00001; UC: GA+AA vs. GG, OR = 1.21, 95%CI, 1.08–1.36, I 2 = 1%, P unadjusted = 0.001, P Bonferroni = 0.005, P FDR = 0.00125). In subgroup analyses by ethnicity, the significant association was found only among Caucasians. However, when grouped by age of onset, positive associations were found both among adults and children. In addition, when stratified by study design and genotyping methods, the risk of CD was significantly associated with the STAT3 rs744166 polymorphism in hospital-based and population-based groups and in SNP Array and SNPlex groups. For UC, significant associations were also found in population-based, PCR-RFLP and SNPlex groups. Moreover, these findings were sufficiently robust to withstand the Bonferroni correction and false discovery rate (FDR).ConclusionThis meta-analysis indicates that carriers of the STAT3 rs744166 ‘A’ allele have a significantly greater risk of CD and UC, especially among Caucasians.
Highlights
As a non-specific, intestinal inflammatory disorder, inflammatory bowel disease (IBD) consists of ulcerative colitis (UC) and Crohn’s disease (CD) clinically
The results indicated that the signal transducer and activator of transcription 3 (STAT3) rs744166 polymorphism was associated with CD and UC susceptibility (CD: GA+AA vs. GG, odds ratios (ORs) = 1.20, 95%confidence intervals (CI), 1.11–1.30, I2 = 0%, Punadjusted,0.00001, PBonferroni,0.00005, PFDR,0.00001; UC: GA+AA vs. GG, OR = 1.21, 95%CI, 1.08–1.36, I2 = 1%, Punadjusted = 0.001, PBonferroni = 0.005, PFDR = 0.00125)
When stratified by study design and genotyping methods, the risk of CD was significantly associated with the STAT3 rs744166 polymorphism in hospital-based and population-based groups and in SNP Array and SNPlex groups
Summary
As a non-specific, intestinal inflammatory disorder, inflammatory bowel disease (IBD) consists of ulcerative colitis (UC) and Crohn’s disease (CD) clinically. With the increasing incidence and prevalence of IBD, there are more studies researching the risk factors and pathogenesis [3]. Approximately 100 IBD-susceptibility loci, including 70 loci specific to CD and 47 specific to UC, have been identified. Their functions include microbe recognition, lymphocyte activation, cytokine signaling, and intestinal epithelial defense [7,8,9]. Many studies have investigated the associations between the signal transducer and activator of transcription 3 (STAT3) in the susceptibility to ulcerative colitis (UC) and Crohn’s disease (CD). This meta-analysis determined the risk of STAT3 rs744166 polymorphism-conferred UC and CD susceptibility
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