Foxp-3 variants are associated with susceptibility to Graves' disease in Chinese population

Regulatory T cells (Tregs) play an indispensable role in autoimmune disorders. FOXP3 controls the development and function of CD4+CD25+ Tregs. Common variants in the FOXP3 gene are believed to alter messenger RNA (mRNA) expression. The aim of the present investigation was to determine whether FOXP3 polymorphisms predispose an individual to the development of Graves' disease (GD) in a Chinese population. A total of 534 GD patients who reported to and/or were admitted to the Department of Endocrinology, People's Hospital of Zhejiang Province, Yuyao, and 630 healthy controls from similar geographical areas were enrolled in this study. FOXP3 polymorphisms (C-2383T, C-3279A, A-3499G, and T+459C) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The relative expression of FOXP3 was assessed by reverse transcription polymerase chain reaction (RT-PCR) in 110 patients and 110 controls. Statistical analysis was performed using GraphPad Prism software. Heterozygote and minor allele (C-2383T, C-3279A, and T+459C) frequencies were significantly higher in GD patients relative to healthy controls. The relative expression of FOXP3 was significantly lower in GD patients than in healthy controls (P<0.0001). Furthermore, FOXP3 expression was significantly associated with FOXP3 polymorphisms (C-2383T, C-3279A, and T+459C): the wild-type allele was associated with higher FOXP3 expression and mutant alleles were associated with lower FOXP3 expression. In conclusion, this study revealed that FOXP3 polymorphisms are correlated with FOXP3 expression and are significantly associated with susceptibility to GD in a Chinese cohort.