A polymorphism of a platelet glycoprotein receptor as an inherited risk factor for coronary thrombosis.
BACKGROUND
Platelet glycoprotein IIb/IIIa is a membrane receptor for fibrinogen and von Willebrand factor, and it has an important role in platelet aggregation. It is known to be involved in the pathogenesis of acute coronary syndromes. Previously, we found a high frequency of a particular polymorphism, PlA2, of the gene encoding glycoprotein IIIa in kindreds with a high prevalence of premature myocardial infarction.


METHODS
To investigate the relation between the PlA2 polymorphism and acute coronary syndromes, we conducted a case-control study of 71 case patients with myocardial infarction or unstable angina and 68 inpatient controls without known heart disease. The groups were matched for age, race, and sex. We used two methods to determine the PlA genotype: reverse dot blot hybridization and allele-specific restriction digestion.


RESULTS
The prevalence of PlA2 was 2.1 times higher among the case patients than among the controls (39.4 percent vs. 19.1 percent, P=0.01). In a subgroup of patients whose disease began before the age of 60 years, the prevalence of PlA2 was 50 percent, a value that was 3.6 times that among control subjects under 60 years of age (13.9 percent, P=0.002). Among subjects with the PlA2 polymorphism, the odds ratio for having a coronary event was 2.8 (95 percent confidence interval, 1.2 to 6.4). In the patients less than 60 years of age at the onset of disease, the odds ratio was 6.2 (95 percent confidence interval, 1.8 to 22.4).


CONCLUSIONS
We observed a strong association between the PlA2 polymorphism of the glycoprotein IIIa gene and acute coronary thrombosis, and this association was strongest in patients who had had coronary events before the age of 60 years.
Weiss
E J
EJ
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Bray
P F
PF
Tayback
M
M
Schulman
S P
SP
Kickler
T S
TS
Becker
L C
LC
Weiss
J L
JL
Gerstenblith
G
G
Goldschmidt-Clermont
P J
PJ
D000208:Acute Disease; D000789:Angina, Unstable / Q000235:genetics; D016022:Case-Control Studies; D003328:Coronary Thrombosis / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors
D019039:Platelet Glycoprotein GPIIb-IIIa Complex