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Bacterial infection (i.e., Streptococcus sanguinis) has been suggested to be related to pathogenesis and/or symptom of Behcet's disease (BD). Toll-like receptor 9 (TLR9) plays an important role in both the innate and adaptive immune systems by recognizing a component of bacterial DNA (i.e., CpG-DNA). Previous studies have demonstrated that single nucleotide polymorphisms (SNPs) in TLR9 were associated with infectious and autoimmune/autoinflammatory diseases. In this study, we detected five SNPs with BD patients in a Japanese population. Allele frequency analysis of the three common SNPs (-1486: T/C (promoter region), 1174: A/G (intron 1), 2848: G/A (exon 2; Pro545Pro)) showed no statistically significant difference between the BD patients and the healthy controls. However, genotyping analysis revealed that the homozygous genotypes -1486CC and 1174GG were significantly more frequent in the BD patients compared to the healthy controls (P = 0.048 and P = 0.027, respectively). The homozygous diplotype distribution C-G-A/C-G-A was significantly more frequent in the BD patients compared to the healthy controls (P = 0.041). For reporter gene assay, the plasmid construct carrying diplotype distribution C-G/C-G of the -1486T/C and 1174A/G SNPs showed significantly higher luciferase activity compared to the plasmid construct carrying diplotype distribution T-A/T-A (P = 0.019). These results suggested an association of the homozygous genotypes and homozygous diplotype configuration of the TLR9 SNPs with susceptibility to BD in the Japanese population.

ASSOCIATION OF THE TOLL-LIKE RECEPTOR 9 GENE POLYMORPHISMS WITH BEHCET'S DISEASE IN A JAPANESE POPULATION