Inflammation and Endothelial Function Relevant Genetic Polymorphisms and Carotid Plaque in Chinese Population

Abstract

Background: Inflammation and endothelial function play important roles in the pathogenesis of atherosclerosis. The genetic influence on carotid atherosclerotic plaque is mostly unclear. The aim of current study was 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 from May 2015 to September 2015. The residents aged ≥ 40 years volunteered to participate in face-to-face survey in 8 communities at random. A total of 2377 subjects with high stroke risk population 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). Finding: Carotid plaques were found in 852 (35.8%) subjects, 454 (53.3%) had stable plaques, 398 (46.7%) had vulnerable plaques. PPARA rs4253655, HABP2 rs7923349 and IL1A rs1609682 were associated with the carotid plaque presence, and NOS2A rs2297518 and PPARA rs4253655 were associated with vulnerable plaque in univariate analysis. GMDR analysis observed that there was a significant gene-gene interaction among HABP2 rs7923349, ITGA2 rs1991013, IL1A rs1609682 and NOS2A rs8081248, and the high-risk interactive genotype among the 4 variants was independently associated with a higher risk for carotid vulnerable plaque after adjusting the covariates (OR, 2.86, 95% CI: 1.32-7.13, P = 0.003). Interpretation: 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 and plaque vulnerability. The high-risk interactive genotype among rs7923349, rs1991013, rs1609682 and rs8081248 was independently associated with a higher risk for vulnerable plaque, and might be potential markers for plaque vulnerability. Funding Statement: This study was supported in part by grants from the Scientific Research Foundation of Sichuan Provincial Health Department (Grant No. 16ZD046), the Sichuan Science and Technology Agency Research Foundation (Grant No.2018JY0164), and Universal Application Program, Health and Family Planning Commission of Sichuan Province in China (Grant No.17PJ084). Declaration of Interests: The authors stated: None. Ethics Approval Statement: The survey protocol was reviewed and approved by the Ethics Committee of the participating hospitals (People’s Hospital of Deyang City, Suining Central Hospital, and the Affiliated Hospital of Southwest Medical University), and informed consent was obtained from all participants during recruitment.