HLA-DRB1, DQA1 and DQB1 diversity in a mixed population of paraná, Southern Brazil

Aim The purpose of this study was to determine the allelic and haplotype frequencies of HLA-DRB1, -DQA1 and -DQB1 in a mixed population from Parana, Brazil. Methods Samples of 733 donors registered in the National Registry of Bone Marrow Donors (REDOME) from the northern/northwestern Parana, Southern Brazil were analyzed. Genotyping of HLA-DRB1 was performed by PCR-SSOP HD (High Definition) with Luminex method (One Lambda®, CA, USA), and of HLA-DQA1 and DQB1 by PCR-SSO (One Lambda ®, CA, USA) medium/high resolution. To resolve ambiguities in HLA-DRB1 and -DQB1, PCR-SSP (One Lambda ®, CA, USA) was used. Allele and haplotype frequencies, Hardy-Weinberg equilibrium (HWE) and linkage disequilibrium (LD) among different loci were determined by software version 3.11 ARLEQUIN. Results The analysis of the total sample 53, 14 and 23 alleles HLA-DRB1, -DQA1 and DQB1 were identified, respectively. For HLA-DRB1 locus, the most frequent were HLA-DRB1∗07:01 (13.16%), ∗03:01 (8.86%), ∗11:01 (8.59%), ∗15:01 (6.07%), ∗13:01 (5.93%) and ∗01:01 (5.86%). For the loci HLA-DQA1 and HLA-DQB1, alleles with the following frequencies were found: HLA-DQA1∗01:02 (16.85%), ∗05:05 (16.10%), ∗01:01 (14.80%), ∗02:01 (13.16%), ∗05:01 (10.77%) and ∗03:01 (10.64%); HLA-DQB1∗03:01 (20.19%), ∗05:01 (13.98%), ∗02:02 (11.93%), ∗03:02 and ∗02:01 (9.55%) and ∗06:01 (8.59%). One hundred seventy-three HLA-DQA1/DQB1 possible haplotypes, with HLA-DQA1∗05:05/DQB1∗03:01 (15.11%), DQA1∗01:01/DQB1∗05:01 (12.89%) and DQA1∗02:01/DQB∗02:02 (11.05%) were the most frequent. We observed 1275 HLA-DRB1/DQA1/DQB1 possible haplotypes and the most common were HLA-DRB1∗07:01/DQA1∗02:01/DQB1∗02:02 (10.30%), DRB1∗03:01/DQA1∗05:01/DQB1∗02:01 (8.39%) and DRB1∗11:01/DQA1∗05:05/DQB1∗03:01 (5.91%). The distribution of HLA alleles was in HWE. For LD analysis, the strength of the associations between the pair wises HLA DRB1-DQA1, DRB1-DQB1, and DQA1-DQB1 was observed, and all of them were statistically significant (P 0.05). The HLA diversity measured by the estimated heterozygosity was very high, 0.948-0.945 for HLA-DRB1, 0.806-0.876 for HLA-DQA1 and 0.888-0.890 for HLA-DQB1. Conclusion The results obtained in this study underscore the importance of using HLA genes as a tool of research of the ethnic composition of populations.