Platelet membrane glycoprotein Ibalpha gene -5T/C Kozak sequence polymorphism as an independent risk factor for the occurrence of coronary thrombosis.

OBJECTIVE

To explore the potential of the GPIbalpha gene variable number tandem repeat (VNTR) and -5T/C Kozak polymorphisms to act as independent risk factors for myocardial infarction.

METHODS

256 patients aged 33-80 years (180 caucasian, 76 Indian Asian) were recruited at cardiac catheterisation for any diagnostic indication, and divided into two groups: group A, with confirmed previous myocardial infarction evident on ECG or ventriculogram (88 patients, 79 men, 9 women) and group B, with no evidence of myocardial infarction (168 patients, 101 men, 67 women).

RESULTS

There was no significant difference in race, age, hypertension, smoking status, or family history between the infarct and non-infarct groups, though there was a significant difference in sex (89.8% male in group A, 60.1% male in group B, p < 0.001). Genotype analysis showed a strong association between the GPIbalpha Kozak homozygous TT genotype and the occurrence of myocardial infarction (group A: TT 85.2%, TC 12.5%, CC 2.3%; group B: TT 67.3%, TC 32.7%, p = 0.001). No significant association was found between myocardial infarction and the GPIbalpha VNTR, although analysis of the CC VNTR genotype against all other GPIbalpha VNTR genotypes showed a marginal association with myocardial infarction (p = 0.059). There was no association between the Kozak sequence polymorphism (p = 0.797) or GPIbalpha VNTR (p = 0.714) and the degree of vessel disease.

CONCLUSIONS

The homozygous TT Kozak genotype may be a significant factor in the outcome of coronary artery disease completed by myocardial infarction. Conversely, the Kozak C allele in the heterozygous state TC may confer some protection against myocardial infarction.