The GPIIIa (β3 integrin) PlA polymorphism in the early development of coronary atherosclerosis

Jussi Mikkelsson, Markus Perola, Antti Penttilä, Pascal J. Goldschmidt-Clermont, Pekka J. Karhunen

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

The GPIIIa (β3 integrin) is an integral part of two glycoprotein receptors - the GPIIb/IIIa fibrinogen receptors in platelets and the GPV/IIIa vitronectin receptors in endothelium and vascular smooth muscle cells (vSMC). The PlA polymorphism of the gene for GPIIIa (β3 integrin) has been suggested to play an important role in the progression of coronary artery disease (CAD) and in coronary thrombosis. Whether the action of the PlA polymorphism is due to differences in platelet aggregability or function of the vSMC and endothelial GPIIIa is not known. The association of the PlA polymorphism with the early, non-complicated atherosclerosis and CAD was studied in the Helsinki Sudden Death Study (HSDS) comprising two independent, autopsy series of altogether 700 middle-aged Caucasian Finnish men (33-70 year) suffering sudden out-of-hospital death. The burden of complicated lesions was greater in men with the A2 allele (heterozygotes or homozygotes for A2) (P=0.01) compared with PlA1/A1 homozygotes in the entire series. To further estimate the role of platelet-independent GPIIIa receptors, we excluded all cases with coronary thrombosis and thrombus-overlaid complicated lesions. In this subset of men, fibrous coronary lesions were more frequent (OR 2.9; P<0.01) in the coronary arteries of PlA1/A1 homozygotes compared with men with the PlA2 allele. Moreover, men with the PlA1/A1 genotype also had more stenotic coronary arteries (P<0.05) compared with men with the A2 allele at this early, non-complicated stage of atherosclerosis. The findings of this study suggest that PlA1/A1 homozygotes may be prone to early atherosclerosis and more rapid progression of stable CAD whereas carriers of the PlA2 allele are more prone to thrombotic complications. We hypothesize that the PlA polymorphism may account for the early atherosclerosis by affecting the function of endothelial and vSMC GPV/IIIa receptors, whereas the PlA polymorphism on platelet GPIIb/IIIa receptors may play a major role in coronary thrombosis.

Original languageEnglish (US)
Pages (from-to)721-727
Number of pages7
JournalAtherosclerosis
Volume154
Issue number3
DOIs
StatePublished - Feb 15 2001

Keywords

  • Atherosclerosis
  • Blood platelets
  • Coronary disease
  • Genetics
  • Integrins
  • Platelet glycoprotein GPIIb-IIIa complex
  • Polymorphism

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Mikkelsson, J., Perola, M., Penttilä, A., Goldschmidt-Clermont, P. J., & Karhunen, P. J. (2001). The GPIIIa (β3 integrin) PlA polymorphism in the early development of coronary atherosclerosis. Atherosclerosis, 154(3), 721-727. https://doi.org/10.1016/S0021-9150(00)00683-3