New insight into the association of apolipoprotein E genetic variants with carotid plaques and intima-media thickness
New insight into the association of apolipoprotein E genetic variants with carotid plaques and intima-media thickness
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DOI：
10.1161/01.str.0000249011.94055.00
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发表时间：
2006-12-01
期刊：
影响因子：
8.3
通讯作者：
Zureik, Mahmoud
中科院分区：
文献类型：
--
作者：
Debett, Stephanie;Lambert, Jean-Charles;Zureik, Mahmoud
背景和目的-颈动脉斑块和颈动脉内膜中层厚度（IMT）升高是血管发病率和死亡率的主要预测因素。我们的目的是测试它们与载脂蛋白 E (apoE) 基因 epsilon 和 - 219G/T 的 2 个多态性的关联。方法 - 该研究对从法国人口中招募的 5856 名年龄 >= 65 岁的受试者进行三城市研究。颈动脉超声检查包括评估颅外颈动脉中的动脉粥样硬化斑块以及测量颈总动脉 (CCA) 中无斑块部位的 IMT。使用基因型和单倍型分析来测试遗传关联。 结果 - 在包括多态性和血管危险因素的多变量分析中，颈动脉斑块在 epsilon 4 纯合子中更常见（调整后的比值比 = 2.12，95% CI = 1.27 至 3.53），而在 epsilon 2 携带者中则不太常见（调整后的比值比 = 0.79，95% CI = 0.66 至 0.95）与 epsilon 3 纯合子相比。对血脂水平进行调整和分层并没有改变这些结果。 epsilon 34 基因型携带者的 CCA-IMT 较高（平均 CCA-IMT = 0.744 mm，而 epsilon 33 基因型携带者为 0.732 mm，P = 0.002），但在排除有颈动脉斑块的受试者后，这种关联消失。 -219 多态性与颈动脉斑块或 CCA-IMT 之间没有发现关联，并且 -219 和 epsilon 之间没有相互作用或顺式效应。结论 - 这项研究在法国老年人群中进行，表明颈动脉斑块与 apoE epsilon 多态性显着相关，独立于 -219 多态性和血管危险因素，特别是血脂水平。
Background and Purpose - Carotid plaques and elevated carotid artery intima-media thickness (IMT) are major predictors of vascular morbidity and mortality. Our aim was to test their association with 2 polymorphisms of the apolipoprotein E (apoE) gene, epsilon and - 219G/T.Methods - The study was performed on 5856 subjects aged >= 65 years recruited from the French population for the Three-City Study. Carotid ultrasound examination included an assessment of atherosclerotic plaques in the extracranial carotid arteries and a measurement of IMT in the common carotid arteries (CCA) at a site free of plaques. The genetic association was tested using genotype and haplotype analyses.Results - In a multivariate analysis including both polymorphisms and vascular risk factors, carotid plaques were more frequent in epsilon 4 homozygotes (adjusted odds ratio = 2.12, 95% CI = 1.27 to 3.53) and less frequent in epsilon 2 carriers (adjusted odds ratio = 0.79, 95% CI = 0.66 to 0.95) compared with epsilon 3 homozygotes. Adjusting for and stratifying on lipid levels did not modify these results. CCA-IMT was higher in carriers of the epsilon 34 genotype (mean CCA-IMT = 0.744 mm versus 0.732 mm for the epsilon 33 genotype, P = 0.002), but the association disappeared after excluding subjects with carotid plaques. No association was found between the -219 polymorphism and either carotid plaques or CCA-IMT, and there was no interaction or cis-effect between -219 and epsilon.Conclusions - This study, conducted on a large population cohort of French elderly, demonstrated that carotid plaques were significantly associated with the apoE epsilon polymorphism independently of the -219 polymorphism and vascular risk factors, in particular lipid levels.