Inflammation and endothelial function relevant genetic polymorphisms and carotid plaque / 中华神经科杂志

ABSTRACT

Objective:To examine the association of carotid plaque with variants in genes involved in inflammation and endothelial function.Methods:This was a multi-center, cross sectional survey in southwestern China. The residents aged ≥40 years and lived in the community for more than six months volunteered to participate in face-to-face survey in eight communities. A total of 2 377 subjects with high stroke risk were enrolled. Carotid plaque and plaque phenotype were assessed by carotid ultrasound. Genotypes of 19 variants in 10 genes related to inflammation and endothelial function were examined. Gene-gene interaction was analyzed by generalized multifactor dimensionality reduction (GMDR).Results:Carotid plaques were found in 852 (35.8%) subjects, of whom 454 (53.3%) had stable plaques, 398 (46.7%) had vulnerable plaques. PPARA rs4253655 ( OR=1.01, 95% CI 1.03-1.82), HABP2rs7923349 ( OR=1.18, 95% CI 1.06-3.11) and IL1A rs1609682 ( OR=1.09, 95% CI1.03-2.87) were associated with the carotid plaque presence, and NOS2Ars2297518 ( OR=1.05, 95% CI 1.02-2.64) and PPARArs4253655 ( OR=1.00, 95% CI 1.01-1.74) were associated with vulnerable plaque in univariate analysis. GMDR analysis showed that there was a significant gene-gene interaction among HABP2rs7923349, ITGA2rs1991013, IL1Ars1609682 and NOS2Ars8081248, and the high-risk interactive genotype among the four variants was independently associated with a higher risk for carotid vulnerable plaque after adjusting the covariates ( OR=2.81, 95% CI 1.32-7.49, P=0.005). Conclusions:Prevalence of carotid plaque was very high in the high risk stroke population in southwestern China. Variants in genes involved in endothelial function and inflammation were associated with the carotid plaque. The high-risk interactive genotype among HABP2rs7923349, ITGA2rs1991013, IL1Ars1609682 and NOS2Ars8081248 was independently associated with a higher risk for vulnerable plaque.