| As one of the important marker of human cell surface, the HLA (Human leukocyte antigen) system is the most complicated human dominant polymorphic genetic system because of its high homogeneity and complicated polymorphism. It differs significantly in different regions and races, which can be regarded as the best sign of colony genetic character and used for investigating disease susceptibility group distribution and disease association study. It plays an important role in aspects of antigen recognition, presentation, immune response and regulation. HLA genes locate in human chromosome 6p21.3 region. HLA class I gene spans approximately 1500 kb, encoding transplanting antigen. HLA class â…¡gene spans approximately 1000 kb, which consists of a lot of immunologically relevant genes too. DNA typing for HLA locus is necessary for donor selection of organ transplantation, individual identification in forensic medicine, disease and HLA association study and anthropological research.The strong association between B27 and Ankylosing Spondylitis(AS) has been known since 1973. It is remarkably consistent across a wide range of ethnic groups in Europe, the Americas, and Asia and the prevalence of AS closely parallels the frequency of B27 in most populations that have been studied. HLA-B27 is a serologic specificity that encompasses 26 different alleles that are involved in the differential association with AS. It is important to investigate which of them are and are not associated with AS, and whether certain subtypes show any preferential association with some of the clinical features or forms of these diseases among the various ethnic/racial populations and geographic regions of the world. This is expected to provide clues as to the mechanism of disease association.In this study ,we investigated class â… and â…¡ HLA-A,B,DRB1 genes by PCR-SSP DNA typing of the Han nationality in Chongqing(3957 blood samples from Chongqing branch of the haematopoietic stem cell donor data bank in China typed) and got a set ofcomplete and exact gene frequence data of HLA alleles. HLA-B27 subtyping was performed by using PCR-SSP to analyze the polymorphism in exons 2 and 3 of the HLA-B27 gene in 126 HLA-B27 positive healthy controls from 3957 donors and to investigate the distribution of HLA-B27 subtypes of Han nationality in Chongqing with AS patients and healthy controls. The results as follows:1. The results of this study showed that 76 HLA specificity alleles were found in Chongqing population. The number of alleles identified was 19 for HLA-A, 42 for HLA-B, 15 for HLA-DR, respectively. The most frequent HLA-A alleles were A*02 (29.37%) , A* 11 (29.1%) and A*24(17.3%). For the HLA-B locus, the most common in descending order were B*46 (14.98%) , B*4001 (12.91% ) and B13 (9.39%) . For the HLA class-H loci,DRBl*09 (16.98%) , DRB1*15 (12.93%) , DRB1*12 (12.18%) andDRBl*04(10.62%) were the most frequent DR alleles.2. In this population, many haplotypes were in a strong positive-linkage disequilibrium. The most frequent haplotypes for HLA-A-B were A2-B46^ A11-B60 and A33-B58, for HLA-A-DR were A2-DR9, Al 1-DR12 and A11-DR15, for HLA-B-DR were B46-DR9> B58-DR17 and B75-DR12. The most frequent haplotypes with strong positive-linkage disequilibrium were A2-B46> A33-B58 and A3O-B13. Compared to other population, distribution of the allele polymorphism of HLA-A, B and DRB1 of Han nationality in Chongqing are genetically very close to those in Southern Han population.3. The strong association between HLA-B27 and AS was confirmed (OR= 815, p<0.0001) by HLA-B27 antigen expression performed in 139 patients with AS, when allele frequencies of HLA-B27 of Han nationality in Chongqing from 3957 haematopoietic stem cell donor used for comparison.4. In the 126 HLA-B27 positive healthy controls, B*2704(73.88%), B*2705 (22.39%) , B*2718 (0.75%) , B*2720 (0.75%) , B*2707 (0.75%) , B*2709 (0.75%) ,B*2702 (0.75%) were found. The distribution of these alleles in the population of AS patients was: B*2704(57.14%), B*2705(32.53%), B*2707(6.34%), B*2702(1.59%), B*2703(0.79%), B*2708(0.79%), B* 2711(0.79%). These results showed B*2704 and B*2705 were the predominant subtypes in Han Nationality Chinese in Chongqing and significant differences from the distribution of B*2704 and B*2707 between AS patients and healthy controls. B*2704 is the subtype most frequently associated with AS inChongqing and while B*2707 is negatively associated with this disease (OR = 0.11, p<0.05).Research characteristics:First time, the HLA allele polymorphism of Han nationality in Chongqing was investigated and a set of complete and exact gene frequence and haplotype frequence data of HLA alleles was provided for population genetic analyses and could be used as control data for HLA disease association.The distribution of HLA-B27 subtypes among healthy people of Han nationality in Chongqing were studied and compared with that of AS patients.lt provided some evidence for association between AS and HLA-B27 subtypes. |
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