Association of two silent polymorphisms of platelet glycoprotein la/lla receptor with risk of myocardial infarction: a case-control study

Background The platelet membrane glycoprotein la/lla plays a major part in platelet function as a primary receptor for collagen. A previous report showed a variation of glycoprotein la/lla receptor density and function associated with two silent and linked polymorphisms (807C/T and 873G/A) within the glycoprotein la gene. Because platelet thrombus formation is implicated in the pathogenesis of acute myocardial infarction, we investigated these polymorphisms among patients who had had a myocardial infarction. Methods We did a 2/1 case-control study including 177 patients (median age 57·0 [range 32–72] years) and 89 controls with same age and sex. Distributions of the 807C/T and 873G/A polymorphisms were investigated by genotyping DNA by PCR, single-strand conformation polymorphism analysis, and sequencing. Findings The prevalence of the homozygous 807T/873A genotype was 2·9 times higher among patients with myocardial infarction than among controls (16·4% vs 5·6%, p=0·022). There was an association between patients homozygous for the 807T/873A allele and myocardial infarction (odds ratio 3·3 [95% CI 1·2–8·8]), which was strongest in a subgroup of smokers. The homozygous 807T/873A genotype remained an independent risk factor for myocardial infarction (p=0·005) when age, sex, smoking, hypertension, diabetes, body-mass index, LDL-cholesterol and HDL-cholesterol, and fibrinogen were adjusted for by logistic regression. Interpretation The 807T/873A homozygosity of the platelet glycoprotein la/lla gene polymorphism, associated with differences in surface collagen receptor density and activity, appears to be an independent risk factor for acute myocardial infarction. Our findings need to be confirmed in a larger, prospective study that includes patients from different populations and cardiovascular risk groups.