Platelet receptor gene Ibα-5T/C Kozak polymorphism may influence the risk of MI, concludes a preliminary UK study. In the prelude to MI platelets attach, through a glycoprotein complex GPIb/IX/V, to von Willebrand factor on plaques in the arterial walls. Four subunits (GPIbα, GPIbβ, GPIX, GPV) comprise the receptor complex, each specified by a single gene; the GPIbα subunit has the binding site for von Willebrand factor. Douglas et al speculated that the GPIbα-5T/C sequence Kozak polymorphism—affecting GPIb/IX/V expression—and GPIbα variable number tandem repeats (VNTRs)—affecting its structure and lengthening the receptor—might alter the risk of MI. GPIbα Kozak polymorphism is a thymine (T) or cytosine (C) at position −5 around the ATG initiator codon; GPIbα VNTR has four variants (A-D) in descending molecular size.

Douglas et al analysed how common these genotypes were in patients aged 33–80 years (180 white, 76 Indian Asian), recruited at cardiac catheterisation, for those with confirmed MI (one group) and without (another group) but otherwise matched for known risk factors.

GPIbα Kozak homozygous TT genotype was strongly linked with MI (infarct group TT 85.2%, TC 12.5%, CC 2.3%; non-infarct group TT 67.3%, TC 32.7%, CC 32.7; p=0.001) as was TT versus TC and CC genotypes. GPIbα VNTR genotypes showed no link, except marginally, between CC and all other genotypes. Neither polymorphism was linked with severity of arterial disease.

TT Kozak genotype may be important in MI, the authors conclude, but confirmation awaits a larger prospective study.