Nucleotide polymorphisms in the α2 gene define multiple alleles that are associated with differences in platelet α2β1 density

Three allelic differences in the alpha(2) gene are associated with expression levels of the alpha(2)beta(1) integrin on the platelet surface, We have previously defined two linked silent polymorphisms in the alpha(2) gene coding region at nucleotides 807 (C or T) and 873 (G or A). We have now identified one rarer nucleotide polymorphism in the coding region at nucleotide 837 (T or C) and four additional linked polymorphisms within the introns that flank these coding sequences. Moreover, we have determined that the alloantigenic Br polymorphism, which resides in a distal coding region at nucleotide 1648, is also linked to the 837 polymorphism. Thus, three cup gene alleles, defined by eight nucleotide polymorphisms, have now been discovered. Allele 1 (807T/837T/873A/Br-b) is associated with increased levels of alpha(2)beta(1); allele 2 (807C/837T/873G/Br-b) and allele 3 (807C/837C/873G/Br-a) are each associated with lower levels of alpha(2)beta(1). Finally, we also show here that the rate of platelet attachment to type I collagen in whole blood under conditions of high shear rate (1,500/s) is proportional to the density of alpha(2)beta(1) receptors on the platelet surface. Thus, the density of platelet alpha(2)beta(1) could have an important impact on platelet adhesion to collagen in whole blood and therefore on platelet function in vivo, contributing to an increased risk of thrombosis or to bleeding in relevant disease states. (C) 1998 by The American Society of Hematology.