Association of the platelet GPIIb/IIIa polymorphism with atherosclerotic plaque morphology: The Atherosclerosis Risk in Communities (ARIC) Study

Anna M. Kucharska-Newton, Keri L. Monda, Stephen Campbell, Patrick T. Bradshaw, Lynne E. Wagenknecht, Eric Boerwinkle, Bruce A. Wasserman, Gerardo Heiss

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Objectives Platelet activation and aggregation play an important role in the pathogenesis of cardiovascular disease. We examined the association of a single nucleotide polymorphism (SNP) in the GPIIIa platelet glycoprotein (Leu33Pro) with carotid artery plaque morphology and with expression of platelet markers using data from the Atherosclerosis Risk in Communities (ARIC) Carotid MRI study.Methods The study sample consisted of 1202 Caucasian members of the ARIC study cohort recruited in 2004-2005 to participate in the Carotid MRI Substudy under stratified sampling based on maximum carotid artery wall thickness. The Leu33Pro polymorphism was identified as SNP rs5918 in the ITGB3 gene. Plaque visualization was accomplished with contrast enhanced MRI examination of the thickest segment of the carotid artery. Expression of platelet markers was measured using fasting whole blood flow cytometry.Results This cross-sectional analysis based on age and gender adjusted weighted linear regression models suggests that those homozygous for the Leu33Pro risk allele (C) have decreased mean and minimum fibrous cap thickness. We did not observe differences in plaque lipid volume or maximum carotid artery wall thickness across SNP rs5918 genotypes. Carriers of the Leu33Pro polymorphism, as compared to major allele homozygotes, had greater percent of platelets expressing P-selectin, a platelet glycoprotein indicating activation status. Prevalent coronary heart disease did not affect estimates of fibrous cap thickness or of platelet activation.Conclusion Our results suggest that individuals with Leu33Pro polymorphism of the GPIIIa glycoprotein may be predisposed to increased risk of atherosclerotic plaque rupture.

Original languageEnglish (US)
Pages (from-to)151-156
Number of pages6
JournalAtherosclerosis
Volume216
Issue number1
DOIs
StatePublished - May 2011
Externally publishedYes

Keywords

  • Atherosclerosis
  • Coronary heart disease
  • Magnetic resonance imaging (MRI)
  • Plaque
  • Platelets

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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