A common polymorphism flanking the ATG initiator codon of GPIb alpha does not affect expression and is not a major risk factor for arterial thrombosis

The platelet membrane,glycoprotein (GP) Ib alpha plays a key role in the in itial formation of thrombi. Polymorphisms (VNTR and HPA-2) in this receptor are associated with increased risk of coronary heart disease (CHD) and cer ebral vascular disease (CVD). We investigated whether a recently described polymorphism (SIR), due to a single base change (T--> C) five nucleotides u pstream the initiator codon of GPIb alpha, mi ht influence the expression o f the protein, and be implicated in the development of arterial thrombosis. One hundred and thirty nine healthy individuals provided blood samples for DNA analysis of platelet GPIb alpha polymorphisms, and for flow cytometric analysis of the surface expression of the receptor. A group of 20 S/R norma l individuals and an identical number of SIS participants, age and sex matc hed, was investigated for the analysis of the density of various platelet r eceptors. The distribution of the S/R polymorphism was also analyzed in two case/control studies including 104 CVD patients, 101 CHD patients, and one control age, sex, and environmental risk factors matched for each case pat ient. Surface density of GPIba: showed no wide variations between individua ls, was not influenced by the presence of S or R alleles, nor associated wi th the VNTR or HPA-2 polymorphisms. The prevalence of the S/R genotype amon g CVD and CHD patients was not distinct from that in the control groups. We conclude that the S/R polymorphism of GPIb alpha flanking the initiator co don of the receptor, does not seem to be associated with surface levels of the protein, and is not an independent risk factor for arterial thrombosis.