High-Resolution Analyses of Human Leukocyte Antigens Allele and Haplotype Frequencies Based on 169,995 Volunteers from the China Bone Marrow Donor Registry Program

Abstract

Allogeneic hematopoietic stem cell transplantation is a widely used and effective therapy for hematopoietic malignant diseases and numerous other disorders. High-resolution human leukocyte antigen (HLA) haplotype frequency distributions not only facilitate individual donor searches but also determine the probability with which a particular patient can find HLA-matched donors in a registry. The frequencies of the HLA-A, -B, -C, -DRB1, and -DQB1 alleles and haplotypes were estimated among 169,995 Chinese volunteers using the sequencing-based typing (SBT) method. Totals of 191 HLA-A, 244 HLA-B, 146 HLA-C, 143 HLA-DRB1 and 47 HLA-DQB1 alleles were observed, which accounted for 6.98%, 7.06%, 6.46%, 9.11% and 7.91%, respectively, of the alleles in each locus in the world (IMGT 3.16 Release, Apr. 2014). Among the 100 most common haplotypes from the 169,995 individuals, nine distinct haplotypes displayed significant regionally specific distributions. Among these, three were predominant in the South China region (i.e., the 20th, 31st, and 81sthaplotypes), another three were predominant in the Southwest China region (i.e., the 68th, 79th, and 95th haplotypes), one was predominant in the South and Southwest China regions (the 18th haplotype), one was relatively common in the Northeast and North China regions (the 94th haplotype), and one was common in the Northeast, North and Northwest China (the 40th haplotype). In conclusion, this is the first to analyze high-resolution HLA diversities across the entire country of China, based on a detailed and complete data set that covered 31 provinces, autonomous regions, and municipalities. Specifically, we also evaluated the HLA matching probabilities within and between geographic regions and analyzed the regional differences in the HLA diversities in China. We believe that the data presented in this study might be useful for unrelated HLA-matched donor searches, donor registry planning, population genetic studies, and anthropogenesis studies.

HLA‐A, HLA‐B and HLA‐DRB1 allele and haplotype frequencies of 10 918 Koreans from bone marrow donor registry in Korea

“…In the previous study on 4128 cord blood units from Koreans, the presence of a null allele was not detected; however, we detected the presence of A*02:53N null allele in this study (AF 0.04%). Presence of the A*02:53N null allele was also detected in large‐scale studies in the Japanese (Ikeda et al ., ) and the Chinese from the China Bone Marrow Donor Registry Program ( n = 169 995) (Zhou et al ., ), occurring at a frequency of 0.01% and 0.05%, respectively. Allele frequencies in worldwide populations from the Allele Frequencies Net Database (AFND) (Santos et al ., ) reveal that it has not been identified in non‐Asian populations.…”

Genetic polymorphism of human leucocyte antigen and susceptibility to multidrug‐resistant and rifampicin‐resistant tuberculosis in Han Chinese from Hubei Province

“…The results revealed the possible synergistic role of HLA‐B*46:01 with HLA‐A*02:01 on the development of MDR/RR‐TB in this population. According to the high‐resolution analyses of HLA allele and haplotype frequencies based on 169,995 volunteers from the China bone marrow donor registry programme, HLA‐A*02:01 (12.290%) was the third most common HLA‐A allele, and HLA‐B*46:01 (10.221%) was the most frequent HLA‐B allele in China (Zhou et al., ). This high frequent haplotype might contribute to the high MDR/RR‐TB incidence in China.…”

A novel HLA‐DRB1*07 allele, HLA‐DRB1*07:01:22, identified in a Chinese individual

“…Currently, there are a total of 2103 HLA‐DRB1 alleles which have been identified and officially named (IPD‐IMGT/HLA Release 3.29, http://www.ebi.ac.uk/ipd/imgt/hla). According to our recent data, HLA‐DRB1*07:01 alleles are commonly found with high frequency (8.911%) in Chinese volunteers. In this study, we reported a novel HLA‐DRB1*07:01 allele, HLA‐DRB1*07:01:22 , which was identified in a Chinese bone marrow donor using a sequence‐based typing (SBT) method.…”