THE FREQUENCY OF HLA-A2 ALLELES IN 5 AMERICAN POPULATION GROUPS.
JM Ellis, J Ng, R Slack, RJ Hartzman and CK Hurley. Departments of Microbiology, Pediatrics, and Biostatistics, Georgetown University Medical Center, Washington, DC and Navy Medical Research Center, Bethesda, MD.
Of the polymorphic Class I HLA loci, the HLA-A2 family is the most polymorphic at the HLA-A locus. HLA-A2 is one of the most frequent antigens in the human population, present in one-third to one-half of individuals. Accurate Class I antigen matching is important in bone marrow and organ transplants to avoid graft versus host disease and rejection. Knowledge of allele frequencies in various population groups can assist in the search to find a suitable transplant donor. The design of peptide-based vaccines can be aided by knowing which HLA-A2 alleles are frequent in a population. A study using direct automated DNA sequencing was undertaken to determine which of the 31 HLA-A2 alleles were present and their frequency in the five major U.S. population groups (Caucasian, African American, Asian/Pacific Islander, Hispanic, and Native American). DNA samples from fifty-nine unrelated individuals serologically typed as HLA-A2 positive, from each of the five ethnic groups (total 295 individuals), were amplified with an HLA-A specific primer set and sequenced. The sample size of 59 statistically gave a 95% chance of detecting a rare allele present in at least 5% of the population. HLA-A*0201 was the most frequent allele in all groups. Caucasians and Native Americans were predominantly A*0201 (95.7% and 94.3% respectively). Asian/Pacific Islanders and Hispanics had the most allelic diversity, possessing 7 and 9 different alleles, respecitvely, with A*0201 the most frequent. African Americans were not as diverse in terms of the number of different alleles present, but were diverse in that a large percentage of the population had a non-A*0201 allele. The allelic composition of each ethnic group varied. Approximately half of the 30 known HLA-A2 alleles were detected, indicating that the undetected alleles may be rare. One novel HLA-A2 allele, A*0231, was characterized from an African American individual, adding to the complexity of this polymorphic allele family.