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Platelet membrane glycoprotein Ibα gene −5T/C Kozak sequence polymorphism as an independent risk factor for the occurrence of coronary thrombosis
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  1. H Douglas1,*,
  2. K Michaelides2,*,
  3. D A Gorog1,
  4. E Durante-Mangoni1,
  5. N Ahmed1,
  6. G J Davies1,
  7. E G D Tuddenham2
  1. 1National Heart and Lung Institute, Hammersmith Hospital NHS Trust, Du Cane Road, London W12 OHS, UK
  2. 2Haemostasis Research Group, MRC Clinical Sciences Centre, Imperial College, Hammersmith Hospital, London, UK
  1. 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

Abstract

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

  • platelet polymorphisms
  • GPIbα
  • Kozak
  • myocardial infarction
  • bp, base pair
  • GP, platelet gycoprotein
  • PCR, polymerase chain reaction
  • VNTR, variable number tandem repeat
  • vWF, von Willebrand factor
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Footnotes

  • * These authors contributed equally to the study

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