ApoE基因多态性与颈动脉粥样硬化斑块稳定性的相关性研究

Correlation of the genetic polymorphism of Apo E and the stability of carotid plaque

目的:通过载脂蛋白E(apolipoprotein E,Apo E)基因多态性的测定,了解其与人颈动脉粥样硬化(carotid atherosclerosis,CAS)发生及斑块易损的相关性。方法:根据颈动脉彩色超声检测结果将238人分为易损斑块组、稳定斑块组和对照组,进行Apo E基因多态性、超敏C反应蛋白(hypersensitive c-reactive protein,Hs-CRP)、基质金属蛋白酶-9(matrix metalloproteinases-9,MMP-9)、单核细胞趋化蛋白-1(monocyte chemoattractant protein-1,MCP-1)的测定,分析ε4等位基因与斑块易损性、颈动脉内中膜厚度(internal-media thickness,IMT)及血清炎性因子的关系。结果:1易损斑块组ε4等位基因频率较对照组高(χ2=5.78,P=0.020)。2ε4等位基因携带者平均IMT较非ε4等位基因携带者为高,二者差异有统计学意义。3调整年龄、性别、血脂等相关因素后,ε4依然是斑块不稳定的独立相关因素。4ε4等位基因携带者Hs-CRP(t=4.868,P=0.000)、MCP-1(t=7.223,P=0.000)较非ε4等位基因携带者高。结论:Apo E基因多态性与颈动脉粥样硬化斑块易损性相关;ε4等位基因携带者罹患易损斑块的概率更高;ε4等位基因携带者体内炎性活动强于非ε4等位基因携带者。Apo E基因遗传多态性除了通过调节血脂来介导动脉粥样硬化,还可能影响体内慢性炎症状态从而加重动脉粥样硬化。

Objective：To investigate the role of genetic polymorphisms of Apo E in carotid atherosclerosis（CAS）and the instability of the plaque. Methods：Totally 238 subjects were divided into 3 groups：instable plaque group,stable plaque group and control group according to the results of carotid ultrasound examination. The genotype of Apo E and serum Apo E concentration was measured. The relationship between the genetic polymorphism of Apo E and the instability of carotid plaque was studied using linear and logistic regression analysis. Results：1The frequency of ε4 allele in the CAS subjects was higher than that of health people（χ2=5.78,P=0.020）.2The average internal-media thickness（IMT）of subjects with ε4 allele was 1.22 mm,which was significant thicker than that of subjects without ε4 allele. 3The Apo E ε4 allele was an independent relative for the instable plaque when age,sex and blood fat were adjusted in logistic regression analysis. 4 The levels of hypersensitive c- reactive protein（t = 4. 868,P = 0. 000） and monocyte chemoattractant protein-1（t=7.223,P=0.000）in serum of subjects with allele ε4 were higher than those in subjects without ε4 allele.Conclusion：Apo E polymorphism is associated with CAS and the instability of plaques. Patients with Apo E4 have severer CAS than subjects without Apo E e4 allele. The genetic polymorphism of Apo E has influenced the arteriosclerosis through adjusting the bloodfat or the chronic inflammation status.