title: Association of the toll-like receptor 9 gene polymorphisms with Behcet's disease in a Japanese population.
abstract: 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.
authors.affiliation: Department of Gastroenterology and Rheumatology, Fukushima Medical University School of Medicine.
authors.forename: Natsumi
authors.initials: N
authors.lastname: Sakamoto
authors.forename: Hideharu
authors.initials: H
authors.lastname: Sekine
authors.forename: Hiroko
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Yukio
authors.initials: Y
authors.lastname: Sato
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Ohira
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology; D044466:Asian People / Q000235:genetics; D001528:Behcet Syndrome / Q000235:genetics* / Q000276:immunology; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D007564:Japan; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D051217:Toll-Like Receptor 9 / Q000235:genetics*; D055815:Young Adult
chemical_list: C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9