Tu Yaqin, Fan Guorun, Zeng Tianshu, Cai Xiong, Kong Wen
Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Oncotarget. 2017 Aug 10;8(58):98993-99002. doi: 10.18632/oncotarget.20114. eCollection 2017 Nov 17.
Graves' disease (GD) is a common autoimmune disorder with a genetic predisposition. There is strong evidence to suggest that both Th1 and Th2 circulating cytokines are involved in the development of GD. In this study, we conducted a meta-analysis to assess the impact of seven variations of five -related genes on the susceptibility to GD. A total of 22 case-control studies involving 5338 GD patients and 6446 healthy controls were included. The results showed that only one SNP rs1800795 in -6 was significantly associated with GD in homozygous model (CC vs. GG: OR = 2.714, 95% CI = 1.047-7.039, = 0.04), heterozygous model (CG vs. GG: OR = 1.295, 95% CI = 1.013-1.655, = 0.039), dominant model (CC+CG vs. GG: OR = 1.418, 95% CI = 1.122-1.793, = 0.003) and additive model (C vs. G: OR = 1.432, 95% CI = 1.087-1.886, p = 0.011).To explain the heterogeneity, we performed the subgroup analysis by ethnicity. The ethnicity stratification revealed that the association between rs1800795 and GD tended to be much stronger for Asian than European population in homozygous, dominant, recessive, and additive models. The remaining 6 SNPs in 4 genes did not show any significant association with GD in any genetic models. Together, our data support that rs1800795 within the -6 gene confers genetic susceptibility for GD. Future large-scale studies are required to validate the associations between -6 and others -related genes and GD.
格雷夫斯病(GD)是一种具有遗传易感性的常见自身免疫性疾病。有充分证据表明,循环中的Th1和Th2细胞因子均参与GD的发病过程。在本研究中,我们进行了一项荟萃分析,以评估五个相关基因的七个变异对GD易感性的影响。总共纳入了22项病例对照研究,涉及5338例GD患者和6446例健康对照。结果显示,仅-6基因中的一个单核苷酸多态性(SNP)rs1800795在纯合模型(CC与GG:比值比[OR]=2.714,95%置信区间[CI]=1.047 - 7.039,P = 0.04)、杂合模型(CG与GG:OR = 1.295,95% CI = 1.013 - 1.655,P = 0.039)、显性模型(CC + CG与GG:OR = 1.418,95% CI = 1.122 - 1.793,P = 0.003)和加性模型(C与G:OR = 1.432,95% CI = 1.087 - 1.886,P = 0.011)中与GD显著相关。为了解释异质性,我们按种族进行了亚组分析。种族分层显示,在纯合、显性、隐性和加性模型中,rs1800795与GD的关联在亚洲人群中往往比欧洲人群更强。4个基因中的其余6个SNP在任何遗传模型中均未显示与GD有任何显著关联。总之,我们的数据支持-6基因内的rs1800795赋予GD遗传易感性。未来需要大规模研究来验证-6基因及其他相关基因与GD之间的关联。