SEQUENCE VARIATION OF HUMAN PLATELET MEMBRANE GLYCOPROTEIN-IIIA ASSOCIATED WITH THE YUK(A) YUK(B) ALLOANTIGEN SYSTEM

The human platelet alloantigens play a prominent role in provoking neonatal alloimmune thrombocytopenic purpura. The frequencies of Yuk(a) and Yuk(b) antigens are 1.7% and 99.9% in the Japanese population, respectively. The Yuk alloantigen system is localized on the human platelet membrane glycoprotein (GP)IIIa. To investigate the molecular structure of Yuk alloantigenic determinants, we amplified GP IIIa cDNAs from Yuk(a/a) and Yuk(b/b) homozygous individuals. A single nucleotide substitution was found at base 526 of GP IIIa cDNA by direct DNA sequencing analysis. The Yuk(b/b) homozygous individuals bore G at this position while the Yuk(a/a) had A. This base change results in the substitution of glutamine in Yuk(a) for arginine in Yuk(b) at amino acid residue 143 of glycoprotein IIIa molecule. Slot blotting analysis using sequence-specific oligonucleotide probes demonstrated that this Arg/Gln polymorphism is associated with the Yuk alloantigen system.