Platelet Pl(A2) allele and incidence of coronary heart disease: results from the Atherosclerosis Risk In Communities (ARIC) Study.
BACKGROUND
The major platelet integrin glycoprotein IIb-IIIa plays a primary role in platelet aggregation and acute thrombus formation at the site of vascular injury. A genetic polymorphism of glycoprotein IIb-IIIa (Pl(A)) has recently been proposed as a potential genetic factor linking to platelet hyperaggregability and increased risk of myocardial infarction. Despite numerous, mostly nonprospective studies, the role of this polymorphism as a clinically relevant, inherited risk factor for coronary heart disease (CHD) is still controversial. The purpose of this study was to determine whether Pl(A2) is a risk factor for incident CHD and whether it is correlated with increased platelet activation in a case-cohort study nested within a prospective epidemiologic investigation.


RESULTS
Blood samples were collected and processed from the Atherosclerosis Risk in Communities Study cohort at the baseline examination (1987 to 1989). They were stored at -80 degrees C. Pl(A1/A2) genotype and plasma beta-thromboglobulin levels were determined in 439 incident CHD cases and a reference cohort sample of 544 (of whom 18 were also CHD cases). The prevalence of the Pl(A2) allele was not different in cases versus noncases. No significant correlation between CHD risk factors and the Pl(A2) allele was noted either. Platelet activation, as measured by plasma beta-thromboglobulin levels, was not enhanced in individuals with the Pl(A2) allele.


CONCLUSIONS
This prospective study indicates that healthy individuals carrying the Pl(A2) allele do not have an increased risk of CHD.
Aleksic
N
N
Division of Hematology and Vascular Biology Research Center, University of Texas-Houston Medical School, Houston, TX 77030, USA.
Juneja
H
H
Folsom
A R
AR
Ahn
C
C
Boerwinkle
E
E
Chambless
L E
LE
Wu
K K
KK
D000483:Alleles; D016824:Antigens, Human Platelet / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D003327:Coronary Disease / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011446:Prospective Studies; D012044:Regression Analysis; D012307:Risk Factors; D016036:Seroepidemiologic Studies; D001620:beta-Thromboglobulin / Q000378:metabolism
D016824:Antigens, Human Platelet; D001620:beta-Thromboglobulin; C083451:human platelet antigen 1b