| Objective:The purpose of this study is to analyze whether the polymorphism of HLA-DRB1-DQB1 and -DPB1 genes is associated with the susceptibility to Tuberculosis (TB) of Han and Kazak nationality population in Xinjiang, China. We also tried to identifiy novel alleles by HLA-typing and sequencing from these samples.Methods:The whole boold samples were collected from 188 subjects (92 TB patients and 96 healthy control) with Han nationality and 135 subjects (45 TB patients and 90 healthy control) with Kazak nationality from Xinjiang, China. The HLA-DRB1,-DQB1 and -DPB1 gene polymorphism was analyzed by PCR and sequencing based typing (SBT) method.Results:1.The results indicated that DRB 1*07:01 and DQB1*03:01 alleles were detected more frequently in cases than that in controls(15.8% vs 8.3%, X2=4.92, P=0.027, P<0.05; 28.3% vs 13.5%, X2=14.144, P=0.000, P<0.05, respectively)The frequencies of the DPB1*02:01 alleles have lower frequencies in cases than that in controls (18.5%vs 28.1%, X2=4.877, P=0.027, P<0.05). The haplotypes of DRB1*11:01-DQB1*03:01-DPB1*05:01, DRB1*09:01-DQB1*03:03-DPB1*05:01,DQB1*03:01-DPB1*05:01,DQB1*03:03-DPB1*0 5:01 were more frequent in cases than that in controls (5.6% vs 1%, X2=5.86, P=0.015, P<0.05; 8.9% vs 1.6%, X2=9.964, P=0.002, P<0.05; 10.9% vs 4.7%, X2=5.045, P=0.025, P<0.05; 15.8% vs 7.5%, X2=6.65, P=0.01, P<0.05; 9.8% vs 2.3%,X2=8.431, P=0.004, P<0.05, respectively).2. There is no significant differences between the frequency of HLA-DRB1 loci in cases and that in controls from Kazak population(P>0.05). The frequencies of DQB1*05:01 and DPB1*04:01 allele showed higher frequencies in cases than that in controls((13.3% vs 5.6%, X2=4.850, P=0.028, P<0.05, OR=2.615,95%CI[1.084-6.312]; 36.7% vs 23.3%, X2=5.317, P=0.021, P<0.05, OR=1.902,95%CI [1.097-3.299], respectively) and DQB1*03:02 allele have lower frequencies among cases than that among controls (3.3% vs11.7%, X2=5.145,P=0.023,P<0.05,OR:0.261 [0.076-0.900]), DRB1*03:01-DQB1*02:01- DPB1*04:01 haplotypes have higher frequencies in cases than that in controls among Kazak people (8.9% vs 2.4%, P=0.023, P<0.05, OR=4.29,95%[1.257-14.664])3. A novel allele was identified and submitted to new allele of the HLA system. This new allele had two nucleotide substitutions at position 227 from A to T,at nt 236 where from T to C. Compared to the most homologous allele HLA-DRB1*16*23, "HLA-DRB1*16:36" was named by HLA committee.Conclusion:1.The frequencies of the DRB1*0701 and DQB1*03:01 among TB patients in the Xinjiang Han population have more frequencies than that along the controls. In addition, DPB1*04:01 may have protective effect among healthy people. It seems likely that the presence of DRB1*09:01-DQB1*03:03-DPB1*05:01、DQB1*03:01-DPB1*05:01、and DQB1*03:03-DPB1*05:01 may be related to a higher risk of tuberculosis disease.2. There is no dramatic differences in terms of the frequencies about DRB1 loci in Kazak population. DQB1*03:02 allele may be linked to the resistance to TB in Kask population. We also observed that DQB1*05:01 and DPB1*04:01 may have the susceptibility; DRB1*03:01-DQB1*02:01-DPB1*04:01 haplotypes were significantly associated with pulmonary tuberculosis among Kazak people.3. A novel allele was identified and named as "HLA-DRB1*16:36"... |
PDF Full Text Request