The Gene Locus Distribution of HLA in the Chinese Population by High Resolution Typing of HLA-A,B,C,DR,DQ and Its Effect on Stem Cell Transplantation.

Allogeneic hematopoietic stem cell transplantation (AHSCT)can potentially cure a variety of hematopoietic and congenital metabolic disorders. Ideally, one would hope to find identical unrelated donors who are genotypically identical to the patients at all HLA loci. To explore distribution of HLA gene subsites in the Chinese population and its effect on AHSCT. High resolution typing of HLA-A,B,Cw,DR,DQ were performed on 101 cases from the data base of China Marrow Donor Program (CMDP) donors and 76 patients (ALL 23cases, CML 32cases, AML 23cases)by using PCR-SSP and PCR-SSO. The HLA subsites with highest gene frequency were A*0201, A*0207, A*1101, A*2402, B*4001,B*4601, C*0102, C*0702, DR*0901, DR*1202,DQ*0301and DQ*0303(PF>0.2). The subsites with secondary high frequency were A*3101,A*3303,B*1301,B*1302,B*1501, B*5101,B*5801,C*0303,C*0304,C*0602,C*0801, DR*0405, DR*0406,DR*0701,DR*0803, DR*1501,DQ*0202,DQ*0302,DQ*0401, DQ*0502, DQ*0601(PF>0.1). The phenotypic frequency of A*1101,B*4601,C*0102,DR*0901, DQ*0303 in the Chinese population was as high as 0.38, Among which B*4601and DR*0901 were the single allele with highest frequency. The gene locus in HLA with linkage disequilibrium were A*0207-B*4601- DR*0901-C*0102-DQ*0301or0303;A*0201-B*4601-DR*0405 or DR*0803- C*0102-DQ*0302orDQ*0502;A*3001-B*1302-DR*0701-C*0602-DQ*0202 and A*3303- B*5801-DR*0901-C*0302-DQ*0303 or DQ*0302, respectively. CMDP demonstrated the effect of HLA-A and B allele matching on the development of severe acute GVHD and on the overall survival rate. HLA-DR matching are less effective than classIfor clinical outcomes. Additionally, the HLA-C mismatch was found to have a synergistic effect on the acute GVHD and survival rate when another HLA locus mismatch coexisted. Our results demonstrated that the frequency distribution of HLA gene subsites is important for selecting more suitably matched donor for HSCT and is helpful for making donor recruitment strategy. As the HLA-Cw played important role on aGVHD occurrence and the failure of BMT, more attention should be paied on HLA-Cw allele in clinical HSCT.