Arg25Pro (c.915G>C) polymorphism of transforming growth factor β1 gene increases the risk of developing Graves' disease.

Abstract

Graves' disease (GD) arises due to complex interactions between genetic and environmental factors. Transforming growth factor β1 (TGFβ1) is required to maintain immune homeostasis, and is implicated in lymphocyte infiltration, thyroid follicular cell hyperplasia, and production of autoantibody in the thyroid gland of patients with GD. The aim of the present study was to investigate the possible association of Leu10Pro (c.869T>C) and Arg25Pro (c.915G>C) single nucleotide polymorphisms (SNPs) of TGFβ1 gene with the occurrence of GD. We analyzed the genotype and allele frequencies of these SNPs in 171 patients with GD and 197 healthy controls using PCR-restriction fragment length polymorphism (RFLP). The distribution of Leu10Pro (c.869T>C) genotype and allele frequencies in the control and GD groups were not significantly different. However, there was a significant increase of Arg25Pro (c.915G>C) C allele frequency in patients with GD compared with healthy controls (p<0.0001, OR=4.77, 95% CI=3.32-7.03). In addition, C allele carrying subjects (CG+CC) had 5.31-fold increased risk for developing GD according to GG homozygotes (p<0.0001, 95% CI=3.43-8.44). No association between polymorphisms and GD phenotypes was observed. This study indicates that the Arg25Pro (c.915G>C) polymorphism of TGFβ1 gene may be related to occurrence of GD.