The prevalence of the platelet glycoprotein IIIa Pl A1/A2 polymorphism in three South African ethnic groups and its effect on platelet function

Abstract

Introduction In South Africa coronary artery disease (CAD) is less common in African than Indian or white subjects. Although the association between CAD and metabolic factors have been well documented, the role of genetic factors is as yet poorly understood. Specific polymorphisms in the platelet membrane glycoprotein (GP) IIIa gene Pl A1/A2, have been implicated in the development of CAD. Methods The prevalence of platelet GPIIIa (Pl A1/A2) polymorphisms and their effect on platelet function was determined in 313 Indian, 267 white and 227 African subjects with and without a history of CAD. Results In subjects without a history of CAD the frequency of the unfavourable Pl A2 allele was 8.0%, 14.8% and 8.7% in the Indian, white and African populations respectively, with the frequency being significantly higher (p < 0.05) in the white than both other groups. The frequency of the Pl A2 allele was higher in subjects with (23.0%) than without (10.0%; p < 0.0001) a history of CAD. Aggregation studies showed that platelets carrying the Pl A2 allele were hypersensitive to the platelet aggregating agonists ADP and collagen and produced a higher amount of TXA 2 when stimulated with low concentrations of both these agonists. Conclusions The positive association observed between the platelet GPIIIa Pl A1/A2 polymorphism and platelet function suggests that the GPIIIa Pl A2 allele may be a genetic factor that contributes to the risk of sudden death from myocardial infarction in the absence of known risk factors but it does not explain ethnic differences in the prevalence of CAD.