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

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

doi:10.1155/2019/6982623

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

Int J Genomics. 2019 Sep 3:2019:6982623. doi: 10.1155/2019/6982623. eCollection 2019.

Authors

Weihua Sun^{1

2}, Xiaomei Zhang², Jing Wu², Wendi Zhao², Shuangxia Zhao³, Minglong Li¹

Affiliations

¹ Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250000 Shandong Province, China.
² Department of Endocrinology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233000 Anhui Province, China.
³ The Core Laboratory in Medical Center of Clinical Research, Department of Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University (SJTU) School of Medicine, Shanghai 200011, China.

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.