Guo C C, Huang W H, Zhang N, Dong F, Jing L P, Liu Y, Ye X G, Xiao D, Ou M L, Zhang B H, Wang M, Liang W K, Yang G, Jing C X
Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, Guangdong, China.
Department of Parasitology, School of Medicine, Jinan University, Guangzhou, Guangdong, China.
Genet Mol Res. 2015 Oct 27;14(4):13221-35. doi: 10.4238/2015.October.26.19.
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.
乳糜泻（CD）是一种常见的自身免疫性疾病，其特征是对摄入的麸质产生增强的免疫反应。IL2/IL21（rs6822844和rs6840978）和SH2B3（rs3184504）的某些基因多态性可能会影响患CD的易感性，尽管其影响尚不清楚。我们对rs6822844、rs6840978和rs3184504多态性与CD风险之间的关联进行了荟萃分析。检索了PubMed、EMBASE和中国知网。如果异质性检验中I(2)<50%，则使用固定效应模型估计每个单核苷酸多态性（SNP）的OR值和95%CI；否则，使用随机效应模型。我们的荟萃分析纳入了来自16个独立样本的12986例CD病例和28733例对照，每个SNP的分析都包含了总数的一个子集。我们发现，IL2/IL21中rs6822844（T对G，OR=0.72，95%CI=0.67-0.78，P<0.001）和rs6840978（T对C，OR=0.76，95%CI=0.71-0.83，P<0.001）的次要等位基因T均显著降低了CD风险。然而，SH2B3中rs3184504的次要等位基因A（A对G，OR=1.18，95%CI=1.12-1.24，P<0.001）显著增加了CD易感性。rs6822844、rs6840978和rs3184504的估计lambda值分别为0.49、0.50和0.53，表明基因型效应的共显性模型最适合这三个SNP。我们的结果支持这三个SNP与CD之间的关联，并为进一步研究提供了有力依据。
