Platelet glycoprotein Ibα and integrin α2β1polymorphisms: gene frequencies and linkage disequilibrium in a population diversity panel

Genetic variants in the GP1BAand ITGA2genes have been proposed as potential modifiers for arterial vascular disease and bleeding disorders. Since ancestry may play an important role in the prevalence of these variants, we sought to determine their allele frequency and linkage disequilibrium in a collection of 1064 DNA samples from 51 ethnic groups. We studied haplotypes of ITGA2defined by single nucleotide substitutions at positions −52, 807, and 1648, and GP1BAvariants defined by sequence changes in positions −5 (Kozak), 1018 (T145M, HPA‐2) and 1285 (VNTR A, B, C and D). Frequency of haplotypes of ITGA2showed considerable variation across the different groups, with a higher prevalence of the haplotype −52C or T/807C/1648A observed in African compared with caucasian and Asian populations. The haplotypes 52C/807T/1648A and −52T/807T/1648A were not observed in caucasians or South Americans. While relative frequencies of the GP1BAKozak alleles were comparable across groups, the methionine allele (HPA‐2b) showed a higher frequency in Africa (0.26) than in the other groups. We also observed a high prevalence of the VNTR B allele in the African and Israeli populations. Haplotype analysis revealed incomplete linkage disequilibrium between the HPA‐2 and VNTR alleles. Incorporation of GP1BAvariants into the set of SNPs already genotyped by the HapMap project disrupted the pre‐existing haplotype block. These data provide a valuable resource for optimal selection of variants best tailored for association studies of vascular disease or bleeding disorders when examining individuals of different ancestral origins.