Naran Nitien H, Chetty Nanthakumarn, Crowther Nigel J
Department of Chemical Pathology, University of the Witwatersrand, Johannesburg, South Africa.
Thromb Res. 2008;123(2):316-23. doi: 10.1016/j.thromres.2008.06.007. Epub 2008 Jul 25.
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.
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.
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.
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.
在南非，非洲人患冠状动脉疾病（CAD）的情况比印度人或白人少。尽管CAD与代谢因素之间的关联已有充分记录，但遗传因素的作用仍知之甚少。血小板膜糖蛋白（GP）IIIa基因Pl(A1/A2)的特定多态性与CAD的发生有关。
在313名有或无CAD病史的印度人、267名白人和227名非洲人中，测定血小板GPIIIa（Pl(A1/A2)）多态性的患病率及其对血小板功能的影响。
在无CAD病史的受试者中，不利的Pl(A2)等位基因频率在印度人、白人和非洲人群中分别为8.0%、14.8%和8.7%，白人中的频率显著高于其他两组（p<0.05）。有CAD病史的受试者中Pl(A2)等位基因频率（23.0%）高于无CAD病史的受试者（10.0%；p<0.0001）。聚集研究表明，携带Pl(A2)等位基因的血小板对血小板聚集激动剂ADP和胶原高度敏感，在低浓度的这两种激动剂刺激下产生更多的血栓素A2（TXA(2)）。
血小板GPIIIa Pl(A1/A2)多态性与血小板功能之间的正相关表明，在没有已知危险因素的情况下，GPIIIa Pl(A2)等位基因可能是导致心肌梗死猝死风险的遗传因素，但它并不能解释CAD患病率的种族差异。
