Sun Weihua, Zhang Xiaomei, Wu Jing, Zhao Wendi, Zhao Shuangxia, Li Minglong
Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250000 Shandong Province, China.
Department of Endocrinology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233000 Anhui Province, China.
Int J Genomics. 2019 Sep 3;2019:6982623. doi: 10.1155/2019/6982623. eCollection 2019.
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, = 0.005; OR = 1.45, 95%CI = 1.21-1.75, < 0.001, respectively). There were negative correlations between GD risk and the haplotype GGCG (OR = 0.56, 95%CI = 0.46-0.67, < 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, = 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, = 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.
本研究旨在探讨格雷夫斯病（GD）与促甲状腺激素受体（TSHR）及细胞毒性T淋巴细胞相关抗原4（CTLA-4）单核苷酸多态性（SNP）之间的关联。我们对来自中国安徽省北部汉族人群的1217名受试者进行了研究。通过使用Fluidigm EP1平台的Taqman探针技术对TSHR基因内的6个SNP（rs179247、rs12101261、rs2284722、rs4903964、rs2300525和rs17111394）以及CTLA-4基因内的4个SNP（rs10197319、rs231726、rs231804和rs1024161）进行基因分型。TSHR等位基因rs179247-G、rs12101261-C和rs4903964-G与GD呈负相关，而rs2284722-A和rs17111394-C等位基因与GD呈正相关。对rs179247、rs2284722、rs12101261和rs4903964位点的TSHR SNP进行分析，得到8种不同的单倍型。GD风险与单倍型AGTA和AATA呈正相关（OR = 1.27，95%CI = 1.07 - 1.50，P = 0.005；OR = 1.45，95%CI = 1.21 - 1.75，P < 0.001）。GD风险与单倍型GGCG呈负相关（OR = 0.56，95%CI = 0.46 - 0.67，P < 0.001）。关于基于TSHR rs2300525和rs17111394位点SNP的单倍型，CC单倍型与GD风险呈正相关（OR = 1.32，95%CI = 1.08 - 1.60，P = 0.006）。对rs231804、rs1024161和rs231726位点的CTLA-4 SNP进行分析，得到4种单倍型，其中AAA与GD风险呈正相关（OR = 1.21，95%CI = 1.02 - 1.43，P = 0.029）。rs179247、rs12101261、rs2284722、rs4903964和rs17111394位点的多态性与GD易感性相关。TSHR和CTLA-4的单倍型也与GD风险相关。
