Association Analysis of TGFBR3 Gene with Vogt-Koyanagi-Harada Disease and Behcet's Disease in the Chinese Han Population

Objectives: Transforming growth factor-beta (TGF-beta) has important regulating roles in the immune system, especially in the differentiation of the type 17 helper T cells (Th17 cells). In this study, we analysed the potential association of the type III TGF-beta receptor (TGFBR3) genetic variations (rs2489188 and rs1805110) in the Chinese Han population for patients with either Vogt-Koyanagi-Harada (VKH) disease or Behcet's disease (BD), two uveitis entities presumably mediated by Th17 cells. Methods: Two single-nucleotide polymorphisms (SNPs), rs2489188 and rs1805110, in TGFBR3 were genotyped in 451 VKH patients, 330 BD patients and 468 healthy controls using a polymerase chain reaction-restriction fragment length polymorphism assay. The association of the two SNPs with both diseases was analysed using the chi-square test. The Bonferroni correction was applied for multiple testing. A binary logistic regression analysis was used to assess the influence of the gender on the association of TGFBR3 polymorphisms with BD. Results: A significantly decreased frequency of rs1805110 CC genotype (corrected P (P-c) = 0.03, odds ratio = 0.617, 95% CI = 0.441-0.863) was observed in BD patients compared with controls. After logistic regression analysis, this association was maintained (P-c = 0.036). Frequencies of genotype and allele of rs2489188 were not different between VKH disease or BD patients and controls. Stratification analysis according to clinical features of VKH disease or BD failed to find any association of the tested SNPs with both diseases. Conclusions: The results suggest that rs1805110 CC genotype in TGFBR3 is probably associated with the protection from BD. The tested two TGFBR3 SNPs are not associated with VKH disease.