| Graves' disease (GD) is thought to be the result of interaction between environmental and genetic factors. Studies have suggested that GD was associated with infections of bacteria (e.g., Yersinia enterocolitica, YE). Toll-like receptor 2, which was reported to play an important role in immune response to YE infection, is a reasonable candidate gene associated with GD. In order to investigate the relationship between TLR2 and the susceptibility of GD, the functional regions of TLR2 locus were amplified using PCR and sequenced in a random sample of 24 subjects. A total of 5 single nucleotides polymorphisms (SNPs) and one -196 to-173 (23bp) insertion/deletion (InDel) polymorphism were detected. All polymorphic sites were consistent with Hardy-Weinberg equilibrium. Further analysis showed that TLR2 in Chinese Han population was not significantly deviated from the neutral model. Linkage disequilibrium analysis showed complete LD between SNP -18945 C/T and SNP -18883 C/G, and strong LD between SNP rs3804099 and SNP rs3804100. Based on this, a case-control association study was conducted in 303 GD patients and 335 controls in Chinese Han population by genotyping the TLR2 polymorphisms found in this study. There was no significant difference between cases and controls in genotypic or allelic frequencies. However, the results also indicated that the frequency of ins/ins genotype of the InDel polymorphisms (P=0.022, OR=1.53,95% CI= 1.08-2.20), A/A genotype (P=0.015, OR=1.53,95%CI= 1.09-2.15) and A allele (P= 0.027; OR=1.37; 95%CI=1.04-1.81) of rs3804100 in patients of early-onset (younger than 40 years old) were significantly higher than that in controls. Our study suggested that the ins/ins genotype of -196 to-173 InDel and A/A genotype of rs3804100 of TLR2 gene might significantly increase the risk of developing GD in patients at the age before 40-years old.
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