title: Association of the platelet GPIIb/IIIa polymorphism with atherosclerotic plaque morphology: the Atherosclerosis Risk in Communities (ARIC) Study.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Our results suggest that individuals with Leu33Pro polymorphism of the GPIIIa glycoprotein may be predisposed to increased risk of atherosclerotic plaque rupture.
authors.affiliation: Department of Epidemiology, University of North Carolina, Chapel Hill, NC, United States. anna newton@unc.edu
authors.forename: Anna M
authors.initials: AM
authors.lastname: Kucharska-Newton
authors.forename: Keri L
authors.initials: KL
authors.lastname: Monda
authors.forename: Stephen
authors.initials: S
authors.lastname: Campbell
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Bradshaw
authors.forename: Lynne E
authors.initials: LE
authors.lastname: Wagenknecht
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Wasserman
authors.forename: Gerardo
authors.initials: G
authors.lastname: Heiss
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002339:Carotid Arteries / Q000473:pathology*; D002340:Carotid Artery Diseases / Q000097:blood / Q000208:ethnology / Q000235:genetics* / Q000473:pathology*; D003287:Contrast Media; D003430:Cross-Sectional Studies; D005260:Female; D005434:Flow Cytometry; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D039661:Integrin beta3 / Q000235:genetics*; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D019007:P-Selectin / Q000097:blood; D010641:Phenotype; D058226:Plaque, Atherosclerotic / Q000097:blood / Q000208:ethnology / Q000235:genetics* / Q000473:pathology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D025341:Principal Component Analysis; D018570:Risk Assessment; D012307:Risk Factors; D012422:Rupture, Spontaneous; D014481:United States / Q000453:epidemiology; D044465:White People / Q000235:genetics
chemical_list: D015415:Biomarkers; D003287:Contrast Media; C061248:ITGB3 protein, human; D039661:Integrin beta3; D019007:P-Selectin; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; C546937:SELP protein, human