title: Higher prevalence of GPIIIa PlA2 polymorphism in siblings of patients with premature coronary heart disease.
abstract: BACKGROUND
  The Pl(A2) polymorphism of GPIIIa has been associated with unstable coronary syndromes in some studies, but the association has remained debated. None of the previous studies have focused on families at high risk. Risk factors tend to cluster within kindreds with high prevalence of premature coronary heart disease (CHD). Therefore, a heightened prevalence of the Pl(A2) polymorphism among siblings of patients with CHD would support the hypothesis that Pl(A2) is linked, directly or indirectly, to CHD.
  
  
  OBJECTIVE
  To measure the prevalence of the Pl(A2) polymorphism among siblings of patients with CHD before the age of 60 years and to seek an association between the Pl(A2) polymorphism and established atherosclerotic and thrombogenic risk factors.
  
  
  METHODS
  From January 1994 to April 1996, we genotyped 116 asymptomatic siblings (60 Caucasians, 56 Afro-Caribbeans) of patients with CHD manifestations before the age of 60 years for the Pl(A) polymorphism (also called HPA-1). A control cohort was used for comparison, consisting of individuals that were matched for race and geographic area but were free of CHD (n = 268, 168 Caucasians and 100 Afro-Caribbeans). In addition, we have characterized the sibling cohort for other atherogenic and thrombogenic risk factors.
  
  
  RESULTS
  The prevalence of Pl(A2)-positive individuals (Pl(A2)[+], Pl(A1/A2) heterozygotes plus Pl(A2/A2) homozygotes) in the sibling cohort was high: 41.4%. When analyzed separately, the prevalence of Pl(A2)(+) siblings was 53.3% among Caucasians and 28.6% among Afro-Caribbeans. There was no association between Pl(A2) and other established atherogenic or thrombogenic risk factors. Interestingly, the clustering of other risk factors was lesser among Pl(A2)(+) siblings than their Pl(A1) counterparts.
  
  
  CONCLUSIONS
  This study supports the hypothesis that the prevalence of Pl(A2)(+) individuals is high in kindreds with premature CHD. Hence, like the established risk factors that tend to cluster in families with premature CHD and contribute strongly to the accelerated atherosclerotic process affecting these individuals, the Pl(A2) polymorphism of GPIIIa may represent an inherited risk that promotes the thromboembolic complications of CHD. That these asymptomatic Pl(A2)(+) siblings had overall less established risk factors than their Pl(A1) counterparts might represent an explanation for why they remained asymptomatic despite their Pl(A2) positivity.
authors.affiliation: Heart and Lung Institute and the Division of Cardiology, College of Medicine and Public Health, The Ohio State University, Columbus 43210, USA. goldschmidt-1@medctr.osu.edu
authors.forename: P J
authors.initials: PJ
authors.lastname: Goldschmidt-Clermont
authors.forename: L D
authors.initials: LD
authors.lastname: Coleman
authors.forename: Y M
authors.initials: YM
authors.lastname: Pham
authors.forename: G E
authors.initials: GE
authors.lastname: Cooke
authors.forename: W S
authors.initials: WS
authors.lastname: Shear
authors.forename: E J
authors.initials: EJ
authors.lastname: Weiss
authors.forename: B G
authors.initials: BG
authors.lastname: Kral
authors.forename: T F
authors.initials: TF
authors.lastname: Moy
authors.forename: R M
authors.initials: RM
authors.lastname: Yook
authors.forename: R S
authors.initials: RS
authors.lastname: Blumenthal
authors.forename: D M
authors.initials: DM
authors.lastname: Becker
authors.forename: L C
authors.initials: LC
authors.lastname: Becker
authors.forename: P F
authors.initials: PF
authors.lastname: Bray
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000235:genetics*; D015331:Cohort Studies; D003327:Coronary Disease / Q000097:blood / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D039661:Integrin beta3; D008297:Male; D008875:Middle Aged; D010979:Platelet Function Tests; D010980:Platelet Membrane Glycoproteins / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics* / Q000502:physiology; D012307:Risk Factors
chemical_list: D015703:Antigens, CD; D039661:Integrin beta3; D010980:Platelet Membrane Glycoproteins