Association of arginase 1 gene polymorphisms with the risk of myocardial infarction and common carotid intima-media thickness
Association of arginase 1 gene polymorphisms with the risk of myocardial infarction and common carotid intima-media thickness
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DOI：
10.1136/jmg.2006.047449
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发表时间：
2007-08-01
影响因子：
4
通讯作者：
Brousseau, Thierry
中科院分区：
文献类型：
--
作者：
Dumont, Julie;Zureik, Mahmoud;Brousseau, Thierry
背景：近年来，人们认为精氨酸酶（ARG） 1在动脉粥样硬化发生中起重要作用。然而，由于其复杂的功能取决于血管细胞类型，其对动脉粥样硬化的影响尚不清楚。目的：探讨动脉粥样硬化相关表型与ARG1基因多态性的关系。方法：从数据库中选择10个ARG1多态性，其中4个单核苷酸多态性（rs2781666、rs2781667、rs2781668、rs17599586）在病例对照研究（350例vs 581例对照）中检测与心肌梗死（MI）的相关性，在963名受试者的独立样本中检测与颈总动脉（CCA）内膜-中膜厚度（CCA- imt）的相关性（Etude du Vieillissement Arteriel （EVA）研究）。结果：rs2781666 G/T多态性的基因型分布在心肌梗死病例和对照组之间存在显著差异（p = 0.005）， GT杂合子(OR （95% CI) 1.5(1.1 ~ 2.0)）和TT纯合子(OR （95% CI) 2.2(1.1 ~ 4.4)）发生心肌梗死的风险持续增加。在EVA研究中，rs2781666多态性也与心肌梗死的替代标志物CCA-IMT升高相关（p = 0.010）。结论：ARG1 rs2781666多态性与心肌梗死和CCA-IMT升高一致相关。这些发现加强了ARG1在血管病理生理中的重要作用的假设。
Background: Recently, it was suggested that arginase ( ARG) 1 plays an important role in atherogenesis. However, because of its complex functions depending on vascular cell type, its impact on atherogenesis remains unclear.Objective: To evaluate the association between ARG1 polymorphisms and phenotypes related to atherosclerosis.Methods: Among 10 ARG1 polymorphisms selected from databases, 4 single-nucleotide polymorphisms ( rs2781666; rs2781667; rs2781668; rs17599586) were tested for association with myocardial infarction ( MI) in a case-control study ( 350 cases vs 581 controls), and with common carotid artery ( CCA) intima-media thickness ( CCA-IMT) in an independent sample of 963 subjects ( Etude du Vieillissement Arteriel ( EVA) study).Results: The genotype distribution of the rs2781666 G/T polymorphism differed significantly between MI cases and controls ( p = 0.005), and the risk of MI was consistently increased for both GT heterozygotes ( OR ( 95% CI) 1.5 ( 1.1 to 2.0)) and TT homozygotes ( OR ( 95% CI) 2.2 ( 1.1 to 4.4)). In the EVA study, the rs2781666 polymorphism was also associated with an increase in CCA-IMT ( p = 0.010), a surrogate marker of MI.Conclusions: The ARG1 rs2781666 polymorphism was consistently associated with MI and an increased CCA-IMT. These findings reinforce the hypothesis of a significant role of ARG1 in vascular pathophysiology.