Genetic associations of the thyroid stimulating hormone receptor gene with Graves diseases and Graves ophthalmopathy: A meta-analysis.

Haibo Xiong,Qian Wang,Hong Yi,Sophia Nadirshina,Xiuqing Wang,Xueqin Liu,Mingxing Wu,Xiyuan Zhou

doi:10.1038/srep30356

Abstract

Graves’ disease (GD) is a common thyroid disease, and Graves ophthalmopathy(GO) is the most common extra-thyroidal manifestation of GD. Genetic associations of the thyroid stimulating hormone receptor (TSHR) gene with GD and GO have been studied in different population groups for a long time. We aimed to obtain a more precise estimation of the effects of TSHR single nucleotide polymorphisms (SNPs) on GD/GO using a meta-analysis. Publications were searched on Pub Med and EMBASE up to December 30, 2015. Eight studies involving three SNPs (rs179247, rs12101255, and rs2268458), which included 4790 cases and 5350 controls, met the selection criteria. The pooled odds ratios (OR) and the 95% confidence intervals (CI) were estimated. SNPs rs179247 (dominant model [GG + GA vs. AA]: OR = 0.66, 95%CI: 0.61–0.73, P = 0.000, I2 = 0%) and rs12101255 (dominant model [TT + TC vs. CC]: OR = 1.67, 95%CI: 1.53–1.83, P = 0.000, I2 = 0%) were significantly associated with GD in all of the genetic models. TSHR rs12101255 and rs2268458 polymorphisms had no association between GO and GD (GD without GO). The results indicate that rs179247 and rs12101255 are likely to be genetic biomarkers for GD. Further studies with different population groups and larger sample sizes are needed to confirm the genetic associations of the TSHR gene with GD/GO.

Highlights

Genetic associations of immunoregulation and thyroid-specific genes with Graves’ disease (GD)/Graves ophthalmopathy (GO) have been studied in different people for a long time
TSHR gene polymorphisms associated with GD/GO susceptibility were found to be located in intron 1
TSHR is a protein that plays a central role in the pathogenesis of GD and GO

Summary

Introduction

Genetic associations of immunoregulation and thyroid-specific genes with GD/GO have been studied in different people for a long time. Three SNPs (rs61747482, rs2234919 and rs1991517) were studied. They were excluded because of their frequent presence in healthy people[13]. Two TSHR SNPs on chromosome 14q31 had been found in a genome-wide association study; these SNPs were closely associated with GD14,15. Though the genetic associations of the TSHR gene have been studied in different ethnic groups for a long time, there is still controversy about the genetic associations for both GD16,17 and GO18. We conducted a meta-analysis to investigate the genetic associations of TSHR gene polymorphisms with GD/GO

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