Abstract
Thromboangiitis obliterans (TAO), also called Buerger's disease, is a chronic peripheral vascular occlusive disease. It is an obliterative vasculitis characterized by arterial thrombosis and strongly associated with tobacco exposure. The pathogenesis and etiology of TAO are not well understood, but genetic factors may be important in its development. A case-control study was undertaken to identify genetic factors potentially involved in the pathogenesis of TAO in a Xinjiang Uyghur population of China, where TAO is common. We ascertained 177 TAO patients by clinical screening and 86 healthy individuals from the HAPMAP database. The genotypes of single-nucleotide polymorphisms (SNPs) of the participants were identified using the Affymetrix Genome-Wide Human SNP Array 6.0 to perform a genome wide association study (GWAS). The association between the SNPs and incidence of TAO was quantified using race stratification exposure. Through a case-control GWAS study 26 SNPs were significantly associated with incidence of TAO following a Bonferroni correction. However, after genomic control correction for population stratification only three of these SNPS were highly significantly associated with TAO: rs376511 in IL17RC (OR = 24.4, 95% CI:8.68 - 68.62, p < 0.0001), rs7632505 in SEMA5B (OR = 29.47, 95% CI:7.16 - 121.3, p < 0.0001), and rs10178082 (OR = 18.09, 95% CI: 6.56 - 49.92, p < 0.0001) showed a significant risk of TAO in the Uyghur population. This study shows an association between these 3 SNPs and susceptibility to TAO in the Uyghur population, suggesting that polymorphisms in the IL-17RC and Sema 5B genes may pre-dispose individuals in this population to development of TAO. These findings require replication.
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