HLA-B*15 gene polymorphism of registered bone marrow from donors in north Chinese Han population typed by PCR-SBT / 中国实验血液学杂志

ABSTRACT

To investigate the characteristics of the allele distribution of HLA-B*15 gene family in Chinese Han population and to study its influence on the selection of clinical transplantation donor, population of a 815 Han in north China from Shaanxi sub-registry of Chinese National Marrow Donor Project was randomly selected and out of them 206 HLA-B*15 positive samples according to the previous known low-resolution typing results were acquired. HLA-B*15 gene polymorphisms of above-mentioned samples and other 17 individuals were analyzed for the first time by polymerase chain reaction sequence-based typing (PCR-SBT) at high-resolution level. The structure differentiation of all HLA-B*15 alleles were analyzed by HLA three-dimensional structure modeling and software Swiss-PdbViewer. The results showed that the distribution of HLA-A, -B, -DRB1 gene of randomly selected 815 samples accorded with Hardy-Weinberg equilibrium and the gene frequency of HLA-B*15 was 0.1379. There were a total of 16 kinds of alleles of HLA-B*15 gene family to be obtained, which belonged to 7 kinds of serologic specificities. HLA-B*1501, B*1511, B*1502 and B*1518 were the major alleles with a frequency of 0.0485, 0.0215, 0.0178 and 0.0160 respectively, and the constituent ratio of their accumulated frequencies was 75.11%. The each frequency of the other 12 kinds of B*15 alleles was lower than 0.0100. Among the homozygote of 10 samples at low/medial-resolution level, there were only 4 samples to be pur sang homozygote of HLA-B*15xx, --at high-resolution level, and all the homozygote were constituted by respective dominating alleles. HLA three-dimensional structure modeling demonstrated that within the same specificity, gentle structure differentiation not only existed, such as B*1501, 1505, 1507, 1525, 1527, 1532 (each RMSD<or=0.02 nm), but also presented significant structure differentiation, such as B*1502, 1511, 1521 and B*1503, 1546 (each RMSD=0.29 nm). However, some alleles belonged to different specificities showed similar structure with RMSD<or=0.02 nm. It is concluded that the characteristics of HLA-B*15 gene polymorphism defined by PCR-SBT with the largest sample size up to now is unique in north Chinese Han population. The study will be helpful to find suitable donors for patients and establish the important foundation for further studying transplantation immunity and population genetics in this area. To select the optimal donor, it is necessary for gene family with high polymorphism like HLA-B*15 to type accurately at high-resolution level.