Correlation of TSHR and CTLA-4 Single Nucleotide Polymorphisms with Graves Disease.

Weihua Sun,Shuangxia Zhao,Wendi Zhao,Jing Wu,Xiaomei Zhang,Minglong Li

doi:10.1155/2019/6982623

Abstract

This study was designed to explore the association between Graves disease (GD) and thyroid-stimulating hormone receptor (TSHR) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) single nucleotide polymorphisms (SNPs). We studied a total of 1217 subjects from a Han population in northern Anhui province in China. Six SNPs within TSHR (rs179247, rs12101261, rs2284722, rs4903964, rs2300525, and rs17111394) and four SNPs within CTLA-4 (rs10197319, rs231726, rs231804, and rs1024161) were genotyped via a Taqman probe technique using a Fluidigm EP1 platform. The TSHR alleles rs179247-G, rs12101261-C, and rs4903964-G were negatively correlated with GD, whereas the rs2284722-A and rs17111394-C alleles were positively correlated with GD. Analyzing TSHR SNPs at rs179247, rs2284722, rs12101261, and rs4903964 yielded 8 different haplotypes. There were positive correlations between GD risk and the haplotypes AGTA and AATA (OR = 1.27, 95%CI = 1.07‐1.50, P = 0.005; OR = 1.45, 95%CI = 1.21‐1.75, P < 0.001, respectively). There were negative correlations between GD risk and the haplotype GGCG (OR = 0.56, 95%CI = 0.46‐0.67, P < 0.001). With respect to haplotypes based on SNPs at the TSHR rs2300525 and rs17111394 loci, the CC haplotype was positively correlated with GD risk (OR = 1.32, 95%CI = 1.08‐1.60, P = 0.006). Analyzing CTLA-4 SNPs at rs231804, rs1024161, and rs231726 yielded four haplotypes, of which AAA was positively correlated with GD risk (OR = 1.21, 95%CI = 1.02‐1.43, P = 0.029). Polymorphisms at rs179247, rs12101261, rs2284722, rs4903964, and rs17111394 were associated with GD susceptibility. Haplotypes of both TSHR and CTLA-4 were additionally related to GD risk.

Highlights

Graves disease (GD) is a common organ-specific autoimmune disease and the most common cause of thyrotoxicosis
Subjects were diagnosed with GD based upon clinical and laboratory examinations that confirmed hyperthyroidism, which was accompanied by symptoms of a high metabolism, diffuse goiter, thyroid ophthalmopathy, and pretibial myxedema, as well as high serum levels of free thyroxine (FT4) and free T3 (FT3), very low levels of circulating thyroidstimulating hormone (TSH), and positive thyrotrophin receptor antibody (TRAb) circulation
A Hardy-Weinberg equilibrium test was performed on the control group, revealing all 10 SNPS in thyroid-stimulating hormone receptor (TSHR) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) to conform to a Hardy-Weinberg equilibrium (P > 0 05) (Table 2)

Summary

Introduction

GD is a common organ-specific autoimmune disease and the most common cause of thyrotoxicosis. GD susceptibility stems from a confluence of genetic, environmental, and immunological factors [1]. In an individual with a genetic predisposition for GD, the disease may develop as a consequence of environmental influences that induce or exacerbate immune dysfunction, leading to the onset of autoimmunity, with clear evidence for the existence of genetic factors predisposing individuals to autoimmune thyroid disease [2, 3]. A recent study from the National Health and Nutritional Examination Survey further sought to identify the role of genetic susceptibility in the etiology of GD [4]. GWAS studies have been very popular in the identification of such susceptibility loci for thyroid autoimmune diseases [5,6,7,8,9,10,11,12,13]

Methods

Results

Conclusion