HLA Allelic and Haplotypic Organization in Common ABO Blood Group Phenotypes: A Single-Center Cross-Sectional...

This study aimed to investigate the relationship between the human leukocyte antigen (HLA) system and ABO blood groups in healthy donors. A comparative analysis of HLA immunogenetic architecture was performed between A Rh(+) and O Rh(+) individuals to examine potential population-level variations.

This retrospective study included 346 unrelated healthy donors registered with the Eskişehir Osmangazi University Tissue Typing Laboratory between 2017 and 2025. Participants were 50.7% female and 49.3% male, with a mean age of 41.2±14.8 years. Detailed HLA immunogenetic analyses were performed for 249 donors, including 142 A Rh(+) and 107 O Rh(+) individuals. The HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 loci were genotyped using the DNA-based polymerase chain reaction sequence-specific oligonucleotide method. Allele frequencies, haplotype distributions, Hardy-Weinberg equilibrium (HWE), and linkage disequilibrium (LD) patterns were analyzed using PyPop software.

Allele distributions were broadly similar between groups. The HLA-DRB1*16 allele was enriched in A Rh(+) donors (8.8% vs. 4.2%, p=0.049), while HLA-B*49, HLA-DPB1*13, and HLA-DPB1*01 alleles were enriched in O Rh(+) donors (p=0.032, 0.022, and 0.015, respectively). LD patterns differed between the groups [A Rh(+): DQB1~DPB1, p=0.038; O Rh(+): HLA-A~DQB1, p=0.019], and all loci were in HWE (p>0.05).

The analysis indicated that A Rh(+) and O Rh(+) donors share a largely similar HLA genetic background, with modest but detectable differences in selected class I and class II HLA alleles and LD patterns. These subtle variations likely reflect minor population heterogeneity rather than distinct ancestry and may aid in donor matching efforts and the interpretation of population-based immunogenetic association studies.