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Genet Mol Res. 2015 Oct 27;14(4):13221-35. doi: 10.4238/2015.October.26.19.

Association between IL2/IL21 and SH2B3 polymorphisms and risk of celiac disease: a meta-analysis.

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Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, Guangdong, China.
Department of Parasitology, School of Medicine, Jinan University, Guangzhou, Guangdong, China.
Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, Guangdong, China


Celiac disease (CD) is a common autoimmune disorder characterized by heightened immunological response to ingested gluten. Certain gene polymorphisms of IL2/IL21 (rs6822844 and rs6840978) and SH2B3 (rs3184504) may influence susceptibility to CD, although the effects remain unclear. We performed a meta-analysis of the associations between rs6822844, rs6840978, and rs3184504 polymorphisms and CD risk. PubMed, EMBASE, and the China National Knowledge Infrastructure were searched. ORs and 95%CIs of each single nucleotide polymorphism (SNP) were estimated using the fixed-effect model if I(2) < 50% in the test of heterogeneity; otherwise, the random-effect model was used. Our meta-analysis included 12,986 CD cases and 28,733 controls from 16 independent samples, and the analysis of each SNP contained a subset of the total. We found that the minor allele T of both rs6822844 (T vs G, OR = 0.72, 95%CI = 0.67-0.78, P < 0.001) and rs6840978 (T vs C, OR = 0.76, 95%CI = 0.71-0.83, P < 0.001) in IL2/IL21 significantly decreased the risk of CD. However, the minor allele A of rs3184504 (A vs G, OR = 1.18, 95%CI = 1.12-1.24, P < 0.001) in SH2B3 significantly increased CD susceptibility. The estimated lambda values were 0.49, 0.50, and 0.53 for rs6822844, rs6840978, and rs3184504, respectively, suggesting that a co-dominant model of genotype effect was most appropriate for the three SNPs. Our results support associations between the three SNPs and CD and provide a strong argument for further research.

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