ABSTRACT
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Subject(s)
Asian People , Genetic Predisposition to Disease , Membrane Glycoproteins/genetics , Polymorphism, Single Nucleotide , Receptors, Interleukin/genetics , Semaphorins/genetics , Thromboangiitis Obliterans , Adolescent , Adult , Asian People/ethnology , Asian People/genetics , Case-Control Studies , China/ethnology , Female , Genome-Wide Association Study , Humans , Male , Middle Aged , Thromboangiitis Obliterans/ethnology , Thromboangiitis Obliterans/geneticsSubject(s)
Thromboangiitis Obliterans/epidemiology , Bias , Female , Humans , Israel/epidemiology , Jews , Male , Thromboangiitis Obliterans/ethnologyABSTRACT
Takayasu's arteritis (TA) and thrombangiitis obliterans (Buerger's disease) are idiopathic, inflammatory arteriopathies with strong indications for the involvement of autoimmunity and host genetic factors in their immunopathogenesis. The exact etiology of these arteriopathies still remains unknown even after almost nine decades of their description. A series of immunogenetic studies conducted worldwide seeking to define genetic factors in governing immune response in these diseases have yielded conflicting results on the involvement of HLA molecules. While an association of HLA-B5 or its molecular subtypes with Takayasu's arteriitis has been emphasized in patients from Japan, Korea and India, no such association has been reported in Mexican and North American patients. On the other hand, a limited data is available on the association of HLA antigens with Buerger's disease. In this article, we provide an overview of the immunogenetics of Buerger's disease and Takayasu's arteriitis in the context of studies in North Indian patients and those in other ethnic groups. Our studies indicate a positive association of Takayasu's arteriitis with the HLA-B5 molecule with no preferential association with its two major subtypes. In Buerger's disease, we have observed a strong positive association with HLA-DRB1*1501 consistent with the findings in Japanese patients. These results suggest an important role of HLA linked factors in governing susceptibility to both arteriopathies.
