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 ApoE and the stability of carotid plaque

摘要:

目的：通过载脂蛋白E（apolipoprotein E，ApoE）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ApoE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：ApoE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。ApoE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。

Abstract:

Objective：To investigate the role of genetic polymorphisms of ApoE 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 ApoE and serum ApoE concentration was measured. The relationship between the genetic polymorphism of ApoE 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 ApoE ε4 allele was an independent relative for the instable plaque when age，sex and blood fat were adjusted in logistic regression analysis. ④The 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：ApoE polymorphism is associated with CAS and the instability of plaques. Patients with ApoE4 have severer CAS than subjects without ApoE e4 allele. The genetic polymorphism of ApoE has influenced the arteriosclerosis through adjusting the blood-fat or the chronic inflammation status.