| [Objective] To investigate the distribution of HLA-DPB1 allele polymorphism in Sichuan Han population; to speculate theoretically the HLA-DPB1 mismatch pattern among unrelated transplant donors in Sichuan Han population; to analyze the rate of HLA-DPB1 allele mismatch among consistent HLA-A,-B, and -DRB1 and their mismatched patterns.[Methods] One thousand ninety seven DNA specimens of Sichuan Han individuals were randomly selected from Sichuan sub-library of China Morrow Donor Program. Nine hundreds and one HLA-A,-B,-DRB1 identical sibling transplant pairs were screened. For all DNA samples, high-resolution HLA-DPB1 sequencing typing was performed using polymerase chain reaction and sequence-based typing (PCR-SBT) combined with Group Specific Sequencing Primers (GSSPs) sequencing to achieve high-resolution genotyping results. The purified sequencing products were sequenced with BigDye Terminator v3.1 Cycle sequencing Kit on an ABI PRISM 3730 DNA Sequencer. Sequences were then analyzed with the uTYPE software. The statistical method to employ to determine the gene frequency of HLA-DPB1 alleles was through direct counting. Chi-square values of allele frequencies from different populations were calculated to test statistical significance. According to T-cell epitopes of DP molecule, HLA-DPB1 mismatch patterns between Sichuan Han unrelated donors and among identical sibling were predicted.[Results] (1) In 1,097 Sichuan Han healthy unrelated individuals, thirty five types of HLA-DPB1 alleles were detected. Alleles with higher frequencies respectively were: HLA-DPB1*05:01:01G (gene frequency, GF= 40.9%),*02:01:02G (GF= 16.1%), *02:02 (GF= 8.4%),*13:01:01G (GF= 7.9%),*04:01:01G (GF= 6.8%). There were also, nine alleles without in the Common and Well-Documented (CWD) HLA alleles list reported by American Society for Histocompatibility and Immunogenetics (ASHI) detected. They were, DPB 1*04:01:15, DPB1*41:01:01, DPB1*48:01, DPB1*100:01, DPB1*25:01, DPB1*71:01, DPB1*91:01, DPB1*93:01 and DPB1*331:01, respectively. Another couple new alleles were separately detected in two cases and officially assigned to be DPB1*363:01 and DPB1*394:01 by the WHO Nomenclature Committee. A Chi-square test was employed to compare HLA-DPB1 alleles in Han populations in Sichuan, Guangzhou and Shandong and Caucasoid population in the United States of America. The distribution of HLA-DPB1 in Sichuan Han population is similar with that in Guangzhou Han population, but the differences between Sichuan Han population and other populations were statistically significant. (2) In transplantation between unrelated Sichuan Han individuals, HLA-DPB1 permissive mismatches accounted for 34.28%. The mismatches in the direction of HvG and the direction of GvH accounted for 17.27%, respectively. Permissive mismatches in TCE3 algorithm and non-permissive mismatches TCE4 algorithm in GvH direction and HvG direction accounted for 15.59%, respectively. (3) The rate of recombination at HLA-DPB1 locus among siblings was 5.2%. Permissive mismatches accounted for 53%, and non-permissive mismatches among HLA-A,-B,-DRB1-identical siblings accounted for 2.44%.[Conclusion] HLA-DPB1 allele polymorphism in Sichuan Han population exhibits rich and unique distribution. Its analysis of HLA-DPB1 TCE mismatch algorithm suggests that HLA-DPB1 non-permissive mismatches between unrelated transplant donors and among identical siblings require clinical attention. Non-permissive mismatches should be avoided when HLA-A,-B,-DRB1 undergo identical sibling hematopoietic cell transplantation. |
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