The Impact of the Glycoprotein Ia Collagen Receptor Subunit A1648G Gene Polymorphism on Coronary Artery Disease and Acute Myocardial Infarction

Hartmut Kroll; Andreas Gardemann; Andreas Fechter; Werner Haberbosch; Sentot Santoso

doi:10.1055/s-0037-1613825

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2000; 83(03): 392-396
DOI: 10.1055/s-0037-1613825

Review Article

Schattauer GmbH

The Impact of the Glycoprotein Ia Collagen Receptor Subunit A₁₆₄₈G Gene Polymorphism on Coronary Artery Disease and Acute Myocardial Infarction

Hartmut Kroll

¹From the Institute for Clinical Immunology and Transfusion Medicine

,

Andreas Gardemann

²From the Institute for Clinical Chemistry and Pathobiochemistry

,

Andreas Fechter

¹From the Institute for Clinical Immunology and Transfusion Medicine

,

Werner Haberbosch

³From the Clinics for Cardiology and Angiology, Justus Liebig University Giessen, Germany

,

Sentot Santoso

¹From the Institute for Clinical Immunology and Transfusion Medicine

› Author Affiliations

Abstract

Summary

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; nonand 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; nonand 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.

Keywords

Glycoprotein Ia/IIa - α₂β₁integrin - risk factor - myocardial infarction - human platelet alloantigen Br^a/Br^b (HPA-5b/a)

Full Text

References

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