Heterogeneity of HLA-DRB1*04 alleles and haplotypes in the Croatian population

Analysis of allele distribution at the HLA-DRB1*04 gene, as one of the frequent ones among Croatians, and their HLA-A-B-DRB1 haplotypes in the Croatian population was performed in this study. Using LABType (R) SSO and PCR-SSP method, 11 DRB1*04 subtypes were observed, of which DRB1*04:01 was the most frequent (28.0%) followed by DRB1*04:02 (26.3%), DRB1*04:03 (22.3%), and DRB1*04:04 (14.2%). The significant haplotypes (with highest P value) for given DRB1*04 allele were the following combinations: HLA-B*15:01-DRB1*04:01, HLA-B*38:01-DRB1*04:02, HLA-B*35:03-DRB1*04:03, HLA-B*35:03-DRB1*04:08, HLA-B*14:01-DRB1*04:04, and HLA-B*49-DRB1*04:05. Marked differences in the distribution of our most frequent haplotypes of HLA-B-DRB1*04 (HLA-B*38:01-DRB1*04:02 and HLA-B*15:01-DRB1*04:01) were found in comparison to other European populations investigated so far. Additionally, comparison of HLA-A-B-DRB1*04 haplotypes showed that although there are similarities in the haplotype structure between our and other populations, there are also noteworthy differences. In summary, the identification of conserved and unusual DRB1*04 haplotypes in the present study of Croats should have important clinical implications for donorrecipient matching in the hematopoietic stem cell transplantation program, help in the understanding of HLA polymorphisms in different European populations, and also prove to be very useful in the determination of possible susceptibility genes involved in HLA-DRB1*04-associated diseases.