A haplotype of Toll-like receptor 1 is associated with resistance to Buerger disease in Japanese

Abstract

Buerger disease (BD) is a vascular disease of unknown etiology characterized by thrombotic occlusion of peripheral arteries. Smoking is a well-known risk factor of BD, but genetic factors may also play an etiological role. Because chronic infection such as oral periodontitis is suggested to be involved in the pathogenesis of BD, polymorphisms in genes responsible for infectious immunity might be associated with BD as genetic factors. In this study, 87 patients and 312 healthy controls were investigated for 26 polymorphisms in the genes for Toll-like receptor (TLR). It was found that single nucleotide polymorphism (SNP) rs5743599 (G>A) in TLR1 showed a nominal association, where the A allele frequency was increased in the patients (0.200 in the patients vs. 0.133 in the controls, odds ratio (OR)=1.63, 95% confidence interval (95%CI)=1.01– 2.62, p=0.042). When the GG genotype was taken as a reference, the GA genotype conferred significantly high risk (OR=1.81, 95%CI=1.03–3.17, p=0.038). In addition, haplotype analysis of TLR1 locus showed that the frequency of a haplotype containing the G allele of rs5743599 was significantly decreased in the patients (0.003 in the patients vs. 0.028 in the controls, OR=0.10, 95%CI=0.01–0.99, permutation p=0.048), suggesting a TLR1 haplotype-linked genetic factor in association with BD. These findings implied that the pathogenesis of BD was at least in part controlled by the innate immunity via TLR10/ TLR1 locus.