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HLA-B*15 diversity in the Korean population
1Department of Clinical Pathology, College of Medicine, Hallym University, Seoul, Korea. leekw@www.hallym.or.kr
Abstract:
Alleles in the HLA-B*15 group encode molecules belonging to several serologic subgroups, B15 (B62, B63, B75, B76, B77) and B70 (B71, B72), representing many of the most problematic types to assign in routine clinical typing laboratories due to their serologic cross-reactivity resulting from structural similarity. More than 25% of Koreans express HLA-B molecules encoded by the HLA-B*15 alleles. To further characterize HLA-B*15 in this population, B*15-specific polymerase chain reaction (PCR) and sequence-specific oligonucleotide probe (SSOP) hybridization analysis using 39 digoxigenin-labeled probes were applied to DNA samples obtained from 237 B15/B70 serologically positive unrelated individuals. Nine B*15 alleles were identified. B*1501 was the most frequent allele (64.8%) followed by B*1511 (14.1%), B*1507 (8.6%), and B*1518 (5.5%) comprising more than 90% of B*15-positive samples. B62 molecules encoded by 4 of the identified alleles (B*1501, B*1507, B*1525, and B*1527) could not be discriminated by serologic reaction patterns. Among the fifteen B15/B70 apparent homozygotes, eight were heterozygotes carrying two different B*15 alleles. Several B*15 alleles exhibited strong associations with specific Cw, DRB1, and A allelic types (e.g., B*1507-Cw3 (22/22); B*1507-DRB1*04 (21/22), B*1507-A24 (17/22)). The data obtained in this study confirmed B*15 diversity in the study population and will be useful in hematopoietic stem cell donor searches as well as in determining the supplementary DNA typing strategy for B15/B70-positive samples in this population.
Insights
Human Leukocyte Antigen (HLA)-B*15 alleles are diverse in Koreans, with B*1501 being most common. This genetic diversity impacts hematopoietic stem cell donor selection and DNA typing strategies for B15/B70 positive individuals.
Area of Science:
- Immunogenetics
- Human Leukocyte Antigen (HLA) complex
- Population genetics
Background:
- HLA-B*15 alleles present challenges in routine clinical typing due to serologic cross-reactivity.
- Over 25% of Koreans express HLA-B molecules encoded by HLA-B*15 alleles, necessitating further characterization.
Purpose of the Study:
- To characterize the diversity of HLA-B*15 alleles in a Korean population.
- To identify specific HLA-B*15 alleles and their frequencies.
- To investigate associations between HLA-B*15 alleles and other HLA loci.
Main Methods:
- Utilized B*15-specific polymerase chain reaction (PCR) and sequence-specific oligonucleotide probe (SSOP) hybridization.
- Analyzed DNA samples from 237 serologically B15/B70 positive Korean individuals.
- Employed 39 digoxigenin-labeled probes for precise allele identification.
Main Results:
- Identified nine distinct HLA-B*15 alleles, with B*1501 (64.8%), B*1511 (14.1%), B*1507 (8.6%), and B*1518 (5.5%) being the most frequent.
- Discovered that B62 molecules, encoded by four alleles, could not be differentiated by serologic methods.
- Revealed that eight of fifteen apparent B15/B70 homozygotes were actually heterozygotes for different B*15 alleles.
- Observed strong associations between specific B*15 alleles and HLA-Cw, DRB1, and A types (e.g., B*1507-Cw3, B*1507-DRB1*04, B*1507-A24).
Conclusions:
- Confirmed significant HLA-B*15 allele diversity within the Korean population.
- Highlighted the limitations of serologic typing for certain HLA-B*15 alleles.
- Emphasized the utility of these findings for optimizing hematopoietic stem cell donor searches and DNA typing strategies in this population.