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

¹ National Heart and Lung Institute, Hammersmith Hospital NHS Trust, Du Cane Road, London W12 OHS, UK
² Haemostasis Research Group, MRC Clinical Sciences Centre, Imperial College, Hammersmith Hospital, London, UK

Correspondence to:
Correspondence to:
Professor EGD Tuddenham, Haemostasis Research Group, MRC Clinical Sciences Centre, The Faculty of Medicine, Imperial College, Hammersmith Hospital, London W12 ONN, UK;
edward.tuddenham{at}csc.mrc.ac.uk

Objective: To explore the potential of the GPIb 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 GPIb 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 GPIb VNTR, although analysis of the CC VNTR genotype against all other GPIb 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 GPIb 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.

Keywords: platelet polymorphisms; GPIb; Kozak; myocardial infarction

Abbreviations: bp, base pair; GP, platelet gycoprotein; PCR, polymerase chain reaction; VNTR, variable number tandem repeat; vWF, von Willebrand factor

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