HLA‐B44 ALLELE FREQUENCIES AND HAPLOTYPIC ASSOCIATIONS IN THREE EUROPEAN POPULATIONS

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Abstract
HLA‐B44 is among the most frequent class I antigens in many populations studied so far. It has been subdivided into seven allelic forms that can only be discriminated by DNA typing. Using a simple PCR/sequence‐specific oligonucleotide hybridization procedure, we have analysed the frequency distribution of B44 subtypes in three European populations from Slovenia, the Netherlands, and Switzerland. B*4402 and B*4403 were by far the predominant alleles, B*4404 and 4405 were rare, while B*4406 and B*4407 were not observed. Interestingly, B*4402 and 4403 occurred with different frequencies in the three populations, with B*4402 being most frequent in the Swiss (65% vs. 57% in the Dutch, and 46.5% in the Slovenes). Of the 139 individuals studied, 60 HLA‐B44 ABDR haplotypes could be determined by family studies. In the respective populations, the linkage disequilibria between B44 and other HLA antigens occurred with different frequencies. A2‐B*4402 haplotypes were very frequent in the Swiss sample, mostly associated with DRB1*0101, 0401 and 1301. B*4402 was more often linked with non‐A2 antigens in the Slovenes (predominantly A24, A28) than in the Swiss and the Dutch. The predominant association of B*4403 was with DR7: this haplotype was very frequent in the Swiss (82% of the B*4403 haplotypes), while lower frequencies were found in the Dutch (72%) and Slovenian (59%) populations. In the Swiss population, more than half of the B44‐DR7 haplotypes were A23‐B*4403‐DR7 (53% of all B*4403 haplotypes). This haplotype was significantly less frequent in the Slovenian (6%) and in the Dutch (14%) populations. The second most frequent B*4403 haplotype in both the Swiss and Slovenes is the A29‐B*4403‐Cw*1601‐DR7 haplotype (17.6 and 29.4%, respectively). Concomitant with the increased frequency of B*4403 in the Slovenes, a higher diversity of non‐DR7 B44 haplotypes was observed in this population (41% of all B*4403 haplotypes). HLA‐B44 oligotyping analysis allowed us to detect B44‐subtype incompatibilities in several AB‐sero, DRB1/B3/B5‐oligo matched unrelated bone marrow donor/patient combinations. The different frequency distributions of HLA‐B44 haplotypes in the three populations analysed in this study argue in favour of local volunteer bone marrow donor recruitment. This might significantly improve the chance of finding a highly matched donor for patients with less frequent A‐B‐DRB1 haplotypes.

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