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

Abstract

To evaluate the relationship between carotid stenosis with variants in genes referred to inflammation and endothelial function. 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). 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). 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.