Abstract
Thyroid stimulating hormone receptor (TSHR) is thought to be a significant candidate for genetic susceptibility to Graves' disease (GD). However, the association between TSHR gene polymorphism and the risk of GD remains controversial. In this study, we investigated the relationship between the two conditions by meta-analysis. We searched all relevant case-control studies in PubMed, Web of Science, CNKI and Wanfang for literature available until May 2015, and chose studies on two single nucleotide polymorphisms (SNPs): rs179247 and rs12101255, within TSHR intron-1. Bias of heterogeneity test among studies was determined by the fixed or random effect pooled measure, and publication bias was examined by modified Begg's and Egger's test. Eight eligible studies with 15 outcomes were involved in this meta-analysis, including 6,976 GD cases and 7,089 controls from China, Japan, Poland, UK and Brazil. Pooled odds ratios (ORs) for allelic comparisons showed that both TSHR rs179247A/G and rs12101255T/C polymorphism had significant association with GD (OR=1.422, 95%CI=1.353–1.495, P<0.001, Pheterogeneity=0.448; OR=1.502, 95%CI: 1.410–1.600, P<0.001, Pheterogeneity=0.642), and the associations were the same under dominant, recessive and co-dominant models. In subgroup analyses, the conclusions are also consistent with all those in Asian, European and South America subgroups (P<0.001). Our meta-analysis revealed a significant association between TSHR rs179247A/G and rs12101255T/C polymorphism with GD in five different populations from Asia, Europe and South America. Further studies are needed in other ethnic backgrounds to independently confirm our findings.
Highlights
Graves' disease (GD) is one of the most common organ-specific endocrine diseases, and a multifactorial disease with genetic susceptibilities and environmental factors
A number of new genes have been reported which may be associated with the etiology of GD, including the methylenetetrahydrofolate reductase (MTHFR) gene[19], CD24 gene[20], mannose-binding lectin2 (MBL2) gene[21], NACHT leucinerich repeat protein 1 (NLRP1) gene[22], and signal transducer and activator of transcription 3 (STAT3) gene[23]
Later studies focused on single nucleotide polymorphisms (SNPs) in intron-1, -7 and -8, and significant associations were found in multi-ethnic origins
Summary
Graves' disease (GD) is one of the most common organ-specific endocrine diseases, and a multifactorial disease with genetic susceptibilities and environmental factors. A number of new genes have been reported which may be associated with the etiology of GD, including the methylenetetrahydrofolate reductase (MTHFR) gene[19], CD24 gene[20], mannose-binding lectin (MBL2) gene[21], NACHT leucinerich repeat protein 1 (NLRP1) gene[22], and signal transducer and activator of transcription 3 (STAT3) gene[23] Among these genes, the TSHR gene is a significant candidate, and failure of tolerance to TSHR is central to the pathogenesis of GD. Recent studies focus on two SNPs, including rs179247 and rs12101255[30,31,32,33,34,35,36,37], within TSHR intron-1, in Asian, European and South America descents, but still generated conflicting results To further examine their potential role in influencing the risk of GD, we performed a meta-analysis on case-control studies to investigate their effects in populations
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