炎症和内皮功能相关基因多态性与颈动脉斑块相关性研究

Inflammation and endothelial function relevant genetic polymorphisms and carotid plaque

目的探讨炎症和内皮功能相关基因多态性与颈动脉斑块的相关性。方法根据中国脑卒中高危人群筛查方案,对四川省8个社区≥40岁且居住时间大于6个月的居民进行筛查。采用颈动脉超声对筛查出的2377名脑卒中高危人群的颈动脉斑块有无、斑块类型进行评估,同时对炎症和内皮功能相关的10个基因19个位点多态性进行检测。通过广义多因子降维法(GMDR)分析这19个基因位点间的交互作用对颈动脉斑块的影响。结果在2377名脑卒中高危人群中,852名(35.8%)发现有颈动脉斑块,其中454名(53.3%)为稳定斑块,398名(46.7%)为易损性斑块。单因素分析发现,PPARArs4253655(OR=1.01,95%CI 1.03~1.82),HABP2rs7923349(OR=1.18,95%CI 1.06~3.11)和IL1Ars1609682(OR=1.09,95%CI 1.03~2.87)与颈动脉斑块相关(均P<0.05);NOS2Ars2297518(OR=1.05,95%CI 1.02~2.64)和PPARArs4253655(OR=1.00,95%CI 1.01~1.74)与易损斑块相关。GMDR分析发现,HABP2rs7923349、ITGA2rs1991013、IL1Ars1609682和NOS2Ars8081248之间存在交互作用。调整协变量和单因素分析有统计学意义的基因型后发现,这4个基因位点高风险交互基因型与颈动脉易损斑块的发生独立相关(OR=2.81,95%CI 1.32~7.49,P=0.005)。结论脑卒中高危人群中颈动脉斑块的患病率高。炎症和内皮功能相关基因位点HABP2rs7923349、ITGA2rs1991013、IL1Ars1609682和NOS2Ars8081248多态性及它们之间的交互作用可能与颈动脉斑块的发生、发展相关。

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%CI 1.03-2.87) 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.