糖蛋白Ia胶原受体亚基A1648G基因多态性对冠状动脉疾病和急性心肌梗死的影响。

The impact of the glycoprotein Ia collagen receptor subunit A1648G gene polymorphism on coronary artery disease and acute myocardial infarction.

作者信息

Kroll H, Gardemann A, Fechter A, Haberbosch W, Santoso S

机构信息

Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University Giessen, Germany.

出版信息

Thromb Haemost. 2000 Mar;83(3):392-6.

PMID:10744142

Abstract

Platelet glycoprotein (GP) Ia is the major receptor for collagen and plays an important role in platelet adhesion and aggregation. Different gene polymorphisms have been identified that induce either various expression levels (C807T) or alterations of the tertiary structure (A1648G) of GPIa. Previously, we could demonstrate an association of the GPIa C807T dimorphism with nonfatal myocardial infarction. We have now analysed the influence of the GPIa A1648G (Br, HPA-5) dimorphism on the risk of coronary artery disease (CAD) and acute myocardial infarction (AMI). DNA samples from 2163 male Caucasian patients who underwent coronary angiography were genotyped by polymerase chain reaction and restriction fragment length analysis. The relation of the GPIa A1648G dimorphism to the extent of CAD was determined by multiple regression analysis with adjustment for coronary risk factors. Odds ratios (OR) as an estimate of relative risk of CAD and AMI and two-tailed p-values were calculated by multiple logistic regression. In the total study sample, no association was detected between the A1648G dimorphism and CAD or AMI. However, upon analysis of low-risk patient subgroups we found an association of the GPIa A1648G polymorphism with the risk and the extent of CAD (patients with high apoAI/apoB ratio: OR 0.59, p = 0.0090; non- and ex-smokers: OR 0.66, p = 0.0131; both inclusion criteria: OR 0.44, p = 0.0003). The relative frequency of the A1648 allele was higher in controls whereas the GG1648 genotype was overrepresented in patients with CAD. This association was also detectable when individuals with low expression levels of GPIa (C807 homozygotes) were analysed (patients with high apoAI/apoB ratio: OR 0.44, p = 0.0045; non- and ex-smokers: OR 0.61, p = 0.0370). Our findings indicate that the A1648G polymorphism of the platelet collagen receptor plays a role in CAD in well defined patient groups.

摘要

血小板糖蛋白（GP）Ia是胶原蛋白的主要受体，在血小板黏附和聚集过程中起重要作用。已发现不同的基因多态性，它们可导致GPIa的表达水平各异（C807T）或三级结构改变（A1648G）。此前，我们已证实GPIa C807T二态性与非致命性心肌梗死有关。我们现在分析了GPIa A1648G（Br，HPA - 5）二态性对冠状动脉疾病（CAD）和急性心肌梗死（AMI）风险的影响。通过聚合酶链反应和限制性片段长度分析，对2163名接受冠状动脉造影的男性白种人患者的DNA样本进行基因分型。通过对冠状动脉危险因素进行校正的多元回归分析，确定GPIa A1648G二态性与CAD程度之间的关系。通过多元逻辑回归计算比值比（OR）作为CAD和AMI相对风险的估计值以及双尾p值。在整个研究样本中，未检测到A1648G二态性与CAD或AMI之间存在关联。然而，在对低风险患者亚组进行分析时，我们发现GPIa A1648G多态性与CAD的风险和程度存在关联（载脂蛋白AI/载脂蛋白B比值高的患者：OR 0.59，p = 0.0090；非吸烟者和已戒烟者：OR 0.66，p = 0.0131；两个纳入标准均符合者：OR 0.44，p = 0.0003）。对照组中A1648等位基因的相对频率较高，而CAD患者中GG1648基因型的比例过高。在分析GPIa低表达水平的个体（C807纯合子）时，也可检测到这种关联（载脂蛋白AI/载脂蛋白B比值高的患者：OR 0.44，p = 0.0045；非吸烟者和已戒烟者：OR 0.61，p = 0.0370）。我们的研究结果表明，血小板胶原蛋白受体的A1648G多态性在特定患者群体的CAD中起作用。