The prevalence of the platelet glycoprotein IIIa Pl(A1/A2) polymorphism in three South African ethnic groups and its effect on platelet function.
BACKGROUND
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.
Naran
Nitien H
NH
Department of Chemical Pathology, University of the Witwatersrand, Johannesburg, South Africa. nitien.naran@nhls.ac.za
Chetty
Nanthakumarn
N
Crowther
Nigel J
NJ
D000244:Adenosine Diphosphate / Q000819:agonists / Q000494:pharmacology; D000483:Alleles; D001792:Blood Platelets / Q000378:metabolism*; D003094:Collagen / Q000819:agonists / Q000494:pharmacology; D003324:Coronary Artery Disease / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D039661:Integrin beta3 / Q000235:genetics*; D008297:Male; D010974:Platelet Aggregation / Q000502:physiology; D011110:Polymorphism, Genetic; D015995:Prevalence; D013019:South Africa / Q000208:ethnology; D013928:Thromboxane A2 / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism; D014505:Urban Population
C061248:ITGB3 protein, human; D039661:Integrin beta3; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; D003094:Collagen