Miao Xuan1, Shuang-Xia Zhao2, Chen-Yan Yan2, Jun Yang3, Ying Li1, Li-Ge Song1, Huai-Dong Song2, Xiu-Zhen Zhang1. 1. Department of Endocrinology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China. 2. 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. 3. Department of Clinical Skill Practice and Training Center, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
Abstract
BACKGROUND: This study aimed to determine independent risk loci of Graves' disease (GD) in the thyroglobulin (TG) region. METHODS: In this two-staged association study, a total of 9,757 patients with GD and 10,626 sex-matched controls were recruited from Chinese Han population. Illumina Human660-Quad BeadChips in the discovery stage and TaqMan SNP Genotyping Assays in the replication stage were used for genotyping. Trend test and logistic regression analysis were performed in this association study. RESULTS: In the discovery stage, rs2294025 and rs7005834 were the most highly associated susceptibility loci with GD in TG. In the replication phase, 7 SNPs, including rs2294025 and rs7005834, were selected for fine-mapping. Finally, we confirmed that rs2294025 and rs7005834 were the independent risk loci of GD in the combined populations. At the same time, there was no significant difference between the risk allele frequencies of rs2294025 and rs7005834 in different clinical phenotypes of GD. CONCLUSIONS: The fine mapping study of thyroglobulin identified two independent SNPs (rs2294025 and rs7005834) for GD susceptibility. However, no significant differences for rs2294025 and rs7005834 were observed, between the different clinical phenotypes of GD, including gender, Graves' ophthalmopathy (GO), and serum levels of thyrotropin receptor antibody, thyroid peroxidase antibody, and thyroglobulin antibody. These results provide a deeper understanding of the association mechanism of thyroglobulin and GD risk. 2019 Annals of Translational Medicine. All rights reserved.
BACKGROUND: This study aimed to determine independent risk loci of Graves' disease (GD) in the thyroglobulin (TG) region. METHODS: In this two-staged association study, a total of 9,757 patients with GD and 10,626 sex-matched controls were recruited from Chinese Han population. Illumina Human660-Quad BeadChips in the discovery stage and TaqMan SNP Genotyping Assays in the replication stage were used for genotyping. Trend test and logistic regression analysis were performed in this association study. RESULTS: In the discovery stage, rs2294025 and rs7005834 were the most highly associated susceptibility loci with GD in TG. In the replication phase, 7 SNPs, including rs2294025 and rs7005834, were selected for fine-mapping. Finally, we confirmed that rs2294025 and rs7005834 were the independent risk loci of GD in the combined populations. At the same time, there was no significant difference between the risk allele frequencies of rs2294025 and rs7005834 in different clinical phenotypes of GD. CONCLUSIONS: The fine mapping study of thyroglobulin identified two independent SNPs (rs2294025 and rs7005834) for GD susceptibility. However, no significant differences for rs2294025 and rs7005834 were observed, between the different clinical phenotypes of GD, including gender, Graves' ophthalmopathy (GO), and serum levels of thyrotropin receptor antibody, thyroid peroxidase antibody, and thyroglobulin antibody. These results provide a deeper understanding of the association mechanism of thyroglobulin and GD risk. 2019 Annals of Translational Medicine. All rights reserved.
Entities:
Keywords:
Graves’ disease (GD); Thyroglobulin; single nucleotide polymorphism (SNP)