Hla‐b44 Allele Frequencies and Haplotypic Associations in Three European Populations

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.

Complete coding sequences and haplotypic associations of HLA‐B*0707, ‐B*1524, ‐B*4405, ‐B*4802, ‐DRB1*0409, ‐DRB1*0411, ‐DRB1*1115, ‐DRB1*1305, and the novel allele ‐DRB1*0709. Group‐specific amplification of cDNA from DRB1 alleles associated to DRB3 and DRB4

“…Studies were performed on both unrelated individuals and families detected B*4405 in 0.7–4.9% of B44‐positive Caucasoids, in association with A2, A24, A30, Cw*0202, DRB1*0101, and DRB1*1601 (22, 23, 26). Subsequent analyses performed in other Caucasoid populations, including the Slovenians and Swiss, confirmed those associations and revealed additional ones to DRB1*1101, DRB1*13, and DRB1*1501 (27). We have isolated identical cDNA sequences of B*4405 from two unrelated donors.…”

Infuence of MHC on odour perception of 43 chemicals and body odour

“…Different allele frequencies were also observed in a comparative study of HLA B44 allelic subtypes and their A-B-DR haplotypes in a Slovenian, Dutch and Swiss population. In contrast to the Dutch and Swiss population, where the B*4402 allele is predominantly linked to HLA-A2 allele, the prevailing linkage in Slovenians is with HLA-A24 and A28 [30]. The B*4403 allele was linked to DR7 allele in 82% of all B*4403 haplotypes in Swiss population and less so in Dutch (72%) and Slovenian (59%) populations [30].…”

“…In contrast to the Dutch and Swiss population, where the B*4402 allele is predominantly linked to HLA-A2 allele, the prevailing linkage in Slovenians is with HLA-A24 and A28 [30]. The B*4403 allele was linked to DR7 allele in 82% of all B*4403 haplotypes in Swiss population and less so in Dutch (72%) and Slovenian (59%) populations [30]. In the Swiss population more than a half of B44-DR7 haplotypes were of one single subtype (A23-B*4403-DR7), while this was significantly lower in Dutch (14%) and even less in Slovenian population (6%) [30].…”

“…The B*4403 allele was linked to DR7 allele in 82% of all B*4403 haplotypes in Swiss population and less so in Dutch (72%) and Slovenian (59%) populations [30]. In the Swiss population more than a half of B44-DR7 haplotypes were of one single subtype (A23-B*4403-DR7), while this was significantly lower in Dutch (14%) and even less in Slovenian population (6%) [30]. All these results clearly show a certain degree of MHC heterogeneity in Slovenian population that is specific as compared to neighbouring nations and others in the world.…”

Strong association between HLA‐Cw*0706 and HLA‐B*44032 in the Bubi population from Equatorial Guinea

“…B*44 was found associated with Cw*07 (66.6%), Cw*14 (23.3%), Cw*04 (6.6%) and Cw*06 (3.3%) ( 2). In Caucasians, associations were shown between B*4402 and Cw*05 and *07 and B*4403 with Cw*04 and *16 ( 4–6). Cw*16 showed strong linkage disequilibrium with B*45 ( 2).…”