The platelet polymorphism PlA2 is a genetic risk factor for myocardial infarction

Authors


Steen Dalby Kristensen MD, DMSc, Head of Cardiology, Department of Cardiology, Aarhus University Hospital, Skejby Sygehus, Brendstrupgaardsvej 100, DK-8200 Aarhus N, Denmark
(fax: 0045 8949 6002; e-mail: steendk@dadlnet.dk).

Abstract.

Objectives.  Platelet glycoprotein (GP) receptor IIb/IIIa plays a key role in the development of myocardial infarction (MI), and PlA2 is a polymorphism in the gene encoding this receptor. The prevalence of PlA2 shows pronounced geographical variation and has to our knowledge not been presented for a Scandinavian population before. Platelets from PlA2-positive individuals show increased aggregability compared with platelets from PlA2-negative individuals, and PlA2 genotypes might be associated with MI. The purpose of this study was to investigate the relation between the PlA2 polymorphism and MI in a large Scandinavian population.

Design.  Case–control study. We included patients with angiographically verified CAD with and without previous MI and a group of healthy individuals matched for age, race, and sex.

Results.  We studied the frequency of PlA2 in 1191 healthy individuals and 1019 patients with coronary artery disease (CAD). Amongst these patients, 529 subjects had suffered an MI previously. PlA2 was present in 28% of healthy individuals, 28% of patients with CAD but no MI, and in 35% of patients with CAD and MI. The difference between healthy individuals and MI patients was significant (P = 0.002). Furthermore, a graded relationship between the number of PlA2 alleles and the risk of MI was seen (P = 0.011). Associations between PlA2 and traditional cardiovascular risk factors as well as mean platelet volume were investigated. We found a significant interaction between PlA2 and serum cholesterol.

Conclusion.  In our Scandinavian study population the common platelet polymorphism PlA2 is significantly associated with an increased risk of MI, but not of CAD. Clinically, typing for PlA2 might have implications for antiplatelet therapy of patients with MI.

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