Inflammation and endothelial function relevant genetic polymorphisms in carotid stenosis in southwestern China.

ABSTRACT

Aim: To evaluate the relationship between carotid stenosis with variants in genes referred to inflammation and endothelial function. Methods: There was a multi-center, cross sectional survey in southwestern China. The eight communities were selected at random in southwestern China. The residents aged ≥40 years volunteered to participate in face-to-face survey. Subjects with at least three of the aforementioned eight stroke related risk factors or a history of stroke were classified as high-risk population for stroke. A total of 2,377 subjects were the high-risk population for stroke in the eight communities, and degree of carotid stenosis was assessed by carotid ultrasound. Genotypes of 6 variants in 3 genes related to inflammation and endothelial function were examined. Gene-gene interaction was analyzed by generalized multifactor dimensionality reduction (GMDR). Results: Carotid stenosis were found in 295 (12.41%) subjects, of whom 51 (17.29%) had moderate or severe stenosis. According to multivariate logistic regression analysis, we found that HABP2rs7923349TT was independent risk factor for carotid stenosis (OR, 1.96, 95% CI 1.22-3.13, P = 0.005) and ITGA2rs1991013AG and HABP2rs7923349TT were independent risk factors for moderate to severe carotid stenosis (OR, 2.28, 95% CI 1.28-4.07, P = 0.005; OR, 2.90, 95% CI 1.19-7.08, P = 0.019). GMDR analysis showed that there was a significant gene-gene interaction between ITGA2 rs4865756 and HABP2 rs7923349, and the high-risk interactive genotype in the two variants was independently associated with a higher risk for carotid stenosis after adjusting the covariates (OR,1. 42, 95% CI 1.10-1.84, P = 0.008). Conclusions: Prevalence of carotid stenosis was very high in the high-risk stroke population in southwestern China. Variants in genes referred in endothelial function were associated with the carotid stenosis. The high-risk interactive genotype in ITGA2 rs4865756 and HABP2 rs7923349 was independently associated with a higher risk for carotid stenosis.