Association of TLR4 and TLR5 gene polymorphisms with Graves' disease in Chinese Cantonese population.

Graves' disease (GD) is postulated to be caused by the combined effects of susceptibility genes and environmental triggers. Toll like receptors (TLRs) play a role in the activation of innate and adaptive immune responses in mammalians. The aim of this study was to evaluate the potential association of TLR4 and TLR5 gene polymorphisms with GD in Chinese Cantonese population. Four single nucleotide polymorphisms (SNPs), rs11536889 and rs7873784 in TLR4, rs2072493 and rs5744174 in TLR5, were evaluated in 332 GD patients and 351 unrelated controls from Chinese Cantonese population. The minor allele C of TLR5 rs5744174 decreased the risk to GD in females (ORC vs. T=0.63; p=0.003; ptrend=0.003). Under a dominant model, rs5744174 conferred a protective effect in all cases (ORCC/CT vs. TT=0.65; p=0.009) or female subset (ORCC/CT vs. TT=0.57; p=0.002). Under a co-dominant model, rs5744174 also conferred a protective effect in all cases (ORTC vs. TT=0.64; p=0.008) and females (ORTC vs. TT=0.57; p=0.002). The haplotype A-C of TLR5 (rs2072493-rs5744174) decreased the risk of GD in females (OR=0.62; p=0.002). The other three SNPs were not found associated with GD. This study provided evidence that polymorphisms in TLR5 might be associated with decreased susceptibility of GD in females.