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The VDR gene confers a genetic predisposition to Graves' disease and Graves' ophthalmopathy in the Southwest Chinese Han population
Gene. 2021 May 30;145750. doi: 10.1016/j.gene.2021.145750
Fangyu Zhou 1, Zhongzhi Liang 2, Xin Wang 1, Guiqin Tan 1, Wenwen Wei 1, Guangbing Zheng 1, Xiaomin Ma 1, Dan Tian 1, Hua Li 3, Hongsong Yu 4
Objective: Graves' disease (GD) is a common autoimmune disease manifesting with diffuse symmetric thyroid gland enlargement, pretibial myxedema, and Graves' ophthalmopathy (GO). Recently, the vitamin D receptor (VDR) gene has been linked to various autoimmune diseases. This study aimed to investigate the association of VDR gene polymorphisms with susceptibility to GD and GO in the Southwest Chinese Han population.
Methods: A two-stage association study was performed in 1,209 controls and 650 GD patients by PCR-RFLP assay. Real-time PCR and ELISA were carried out to quantify gene expression and cytokine production.
Results: The first-stage study showed that the frequency of VDR/Apa I AA genotype was significantly increased in GD (Pc = 1.67×10-2, OR = 1.98). The second-stage and combined studies confirmed the association of VDR/Apa I with GD (AA genotype: Pc = 3.45×10-4, OR = 1.87; A allele: Pc = 2.62×10-2, OR = 1.20). The stratification analysis showed that GO patients had a higher frequency of the VDR/Apa I AA genotype (Pc = 8.69×10-5, OR = 2.84). Functional experiments showed a decreased VDR expression and TGF-β1 production as well as an increased IL-17 production in VDR/Apa I AA genotype carriers.
Conclusion: The VDR/Apa I polymorphism is significantly associated with GD and GO, and it may be involved in the development of GD and GO by influencing VDR mRNA expression levels and the secretion levels of cytokines.
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