The prevalence of the platelet glycoprotein IIIa PlA1/A2 polymorphism in three South African ethnic groups and its effect on platelet function

IntroductionIn 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 PlA1/A2, have been implicated in the development of CAD.MethodsThe prevalence of platelet GPIIIa (PlA1/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.ResultsIn subjects without a history of CAD the frequency of the unfavourable PlA2 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 PlA2 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 PlA2 allele were hypersensitive to the platelet aggregating agonists ADP and collagen and produced a higher amount of TXA2 when stimulated with low concentrations of both these agonists.ConclusionsThe positive association observed between the platelet GPIIIa PlA1/A2 polymorphism and platelet function suggests that the GPIIIa PlA2 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.