The HPA-15 (Gov) Platelet Alloantigen System: Allele Frequencies in the Canadian Population.
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abstract
AbstractHuman platelet antigens (HPAs) are genetically defined polymorphisms expressed on plasma membrane proteins. Alloimmunization following exposure to the incompatible antigen during pregnancy, or following transfusion or transplantation, can cause severe thrombocytopenia and bleeding. The Gov-a/Gov-b biallelic system is expressed on CD109, a 175kD glyco sylphosphatidylinositol-anchored glycoprotein found on platelets, endothelial cells, and activated T-cells (Kelton, 1990; Smith, 1995). Alloimmunization to Gov-a/b is implicated in neonatal alloimmune thrombocytopenia (NAT) and post-transfusion purpura (PTP), and anti-Gov antibodies have been found in polytransfused patients. The Gov-a/Gov-b alleles are encoded by an A-C single nucleotide polymorphism (SNP) at position 2108, resulting in a Tyr682Ser substitution in CD109. Sequence analysis determined that CD109 is a member of the alpha 2 macroglobulin/C3, C4, C5 family of thioester-containing proteins (Lin, 2002). The Gov antigen frequencies are expressed almost equally in the population, and European and Asian studies determined that the Gov-b allele was expressed slightly more often than the Gov-a. Based on these studies the Gov-a/Gov-b antigens were assigned to the HPA-15 system (HPA-15a/15b = Gov-b/Gov-a). South American studies found similar gene frequencies in the general population, but significantly higher frequencies for HPA-15a (0.78) in aboriginal populations (Cardone, 2004). No larger North American studies have been reported since the original report of the Gov allele frequencies based on a limited number of platelet donors (Gov-a: 0.532; Gov-b: 0.468, n=33). We used the polymerase chain reaction with sequence-specific primers (PCR-SSP) to investigate the HPA-15 allele frequencies in the Canadian population. DNA from 273 blood donors was tested using PCR-SSP. The frequency of genotypes HPA-15a/15a, 15a/15b, 15b/15b was found to be 27.84, 49.45, and 22.71 respectively. Thus the allele frequencies for the Canadian population were determined to be 0.517 for HPA-15a and 0.483 for HPA-15b. This data is similar to the frequencies reported among some European studies, and supports evidence that the HPA-15a (Gov-b) allele is expressed slightly more frequently in the general population. Initial reports investigating the Gov alloantigens localized the polymorphism to a novel platelet protein, CD109, and lack of sequence data prevented the use of genotyping studies. The original studies of the Gov antigens, which share almost equal distribution, were limited by available alloantisera and complex screening technologies. The results from this report support the relative allele frequencies for the HPA-15a/15b (Gov-b/Gov-a) antigen system, and emphasize the importance of using genotyping studies to determine allele frequencies.
