We explored the association between HLA-B and HLA-DRB1 polymorphisms and reviewed clinical characteristics of systemic lupus erythematosus(SLE)in Han population in Yunnan,China.Methods:There were 295 patients and 265 ...We explored the association between HLA-B and HLA-DRB1 polymorphisms and reviewed clinical characteristics of systemic lupus erythematosus(SLE)in Han population in Yunnan,China.Methods:There were 295 patients and 265 healthy control subjects(HCs)enrolled in the study.Clinical data and blood samples were collected from the patients.The HLA-B and HLA-DRB1 genotypes were detected in SLE patients and HCs.Results:A total of 74 genotypes on HLA-B loci were determined in 288 patients as well as 57 genotypes in 265 HCs.The results showed SLE was associated with the HLA-B*40:01 and HLA-DRB1*08:03 alleles,and the HLAB*46:01,HLA-DRB1*12:02,DRB1*04:03,DRB1*14:01,DRB1*04:06,and DRB1*11:01 alleles were less likely to appear in SLE patients.Additionally,HLA-B*07:02 and B*40:06 were associated with disease activity.HLADRB1*03:01,DRB1*13:02,and DRB1*12:01 were associated with proteinuria.Furthermore,HLA-B*51:01,B*13:02,B*38:02,B*35:01,HLA-DRB1*15:02,DRB1*15:04,DRB1*15:01,and DRB1*08:03 were correlated with inflammatory factors and immune dysfunction.HLA-B*15:25 was related to the production of multiple antibodies.HLA-DRB1*12:02 might be a protective factor for pancytopenia.The haplotype of HLA-B*40:01/DRB1*08:03 was linked with SLE.Conclusion:SLE in Han population in Yunnan province was associated with the HLA-B*40:01 and HLA-DRB1*08:03 alleles,and the haplotype HLAB*40:01/DRB1*08:03.Several alleles were associated with inflammation,immune disorders,and organ involvement in SLE.Those alleles might be potential genetic markers of SLE.展开更多
Human Leukocyte Antigens (HLAs) play an important role in host immune responses to infectious pathogens, and influence organ transplantation, cancer and autoimmune diseases. In this study we conducted a high resolutio...Human Leukocyte Antigens (HLAs) play an important role in host immune responses to infectious pathogens, and influence organ transplantation, cancer and autoimmune diseases. In this study we conducted a high resolution, sequence-based genotyping of HLA class I and class II genes of more than 2000 women from Kenya, eastern Tanzania and southern Uganda around Lake Victoria and analyzed their allele, phenotype and haplotype frequencies. A considerable genetic diversity was observed at both class I and II loci. A total of 79 HLA-A, 113 HLA-B, 53 HLA-C, 25 HLA-DPA1, 60 HLA-DPB1, 15 HLA-DQA1, 44 HLA-DQB1 and 38 HLA-DRB1 alleles have been identified. The most common class I alleles were A * 02:01:01 (10.90%), B * 58:02 (8.79%), and C * 06:02:01 (16.98%). The most common class II alleles were DPA1*01:03:01 (40.60%), DPB1 * 01:01:01 (23.45%), DQA1 * 01:02:01 (31.03%), DQB1 * 03:01:01 (21.79%), DRB1 * 11:01:02 (11.65%), DRB3 * 02:02:01 (31.65%), DRB4 * 01:01:01 (10.50%), and DRB5 * 01:01:01 (10.50%). Higher than expected homozygosity was observed at HLA-B (P = 0.022), DQA1 (P = 0.004), DQB1 (P = 0.023), and DRB1 (P = 0.0006) loci. The allele frequency distribution of this population is very similar to the ones observed in other sub-Saharan populations with the exception of lower frequencies of A * 23 (5.55% versus 11.21%) and DQA1 * 03 (4.79% versus 11.72%), and higher frequencies of DPB1 * 30 (2.26% versus 0.37%) and DRB1 * 11 (21.51% versus 15.89%). The knowledge of the diversity and allele/ phenotype frequencies of the HLA alleles of this east African population, can contribute to the understanding of how host genetic factors influence disease susceptibility and effective anti-retroviral treatment of HIV infections and future vaccine trials.展开更多
基金National Natural Science Foundation of China,Grant/Award Numbers:81760296,81460256,81160379。
文摘We explored the association between HLA-B and HLA-DRB1 polymorphisms and reviewed clinical characteristics of systemic lupus erythematosus(SLE)in Han population in Yunnan,China.Methods:There were 295 patients and 265 healthy control subjects(HCs)enrolled in the study.Clinical data and blood samples were collected from the patients.The HLA-B and HLA-DRB1 genotypes were detected in SLE patients and HCs.Results:A total of 74 genotypes on HLA-B loci were determined in 288 patients as well as 57 genotypes in 265 HCs.The results showed SLE was associated with the HLA-B*40:01 and HLA-DRB1*08:03 alleles,and the HLAB*46:01,HLA-DRB1*12:02,DRB1*04:03,DRB1*14:01,DRB1*04:06,and DRB1*11:01 alleles were less likely to appear in SLE patients.Additionally,HLA-B*07:02 and B*40:06 were associated with disease activity.HLADRB1*03:01,DRB1*13:02,and DRB1*12:01 were associated with proteinuria.Furthermore,HLA-B*51:01,B*13:02,B*38:02,B*35:01,HLA-DRB1*15:02,DRB1*15:04,DRB1*15:01,and DRB1*08:03 were correlated with inflammatory factors and immune dysfunction.HLA-B*15:25 was related to the production of multiple antibodies.HLA-DRB1*12:02 might be a protective factor for pancytopenia.The haplotype of HLA-B*40:01/DRB1*08:03 was linked with SLE.Conclusion:SLE in Han population in Yunnan province was associated with the HLA-B*40:01 and HLA-DRB1*08:03 alleles,and the haplotype HLAB*40:01/DRB1*08:03.Several alleles were associated with inflammation,immune disorders,and organ involvement in SLE.Those alleles might be potential genetic markers of SLE.
文摘Human Leukocyte Antigens (HLAs) play an important role in host immune responses to infectious pathogens, and influence organ transplantation, cancer and autoimmune diseases. In this study we conducted a high resolution, sequence-based genotyping of HLA class I and class II genes of more than 2000 women from Kenya, eastern Tanzania and southern Uganda around Lake Victoria and analyzed their allele, phenotype and haplotype frequencies. A considerable genetic diversity was observed at both class I and II loci. A total of 79 HLA-A, 113 HLA-B, 53 HLA-C, 25 HLA-DPA1, 60 HLA-DPB1, 15 HLA-DQA1, 44 HLA-DQB1 and 38 HLA-DRB1 alleles have been identified. The most common class I alleles were A * 02:01:01 (10.90%), B * 58:02 (8.79%), and C * 06:02:01 (16.98%). The most common class II alleles were DPA1*01:03:01 (40.60%), DPB1 * 01:01:01 (23.45%), DQA1 * 01:02:01 (31.03%), DQB1 * 03:01:01 (21.79%), DRB1 * 11:01:02 (11.65%), DRB3 * 02:02:01 (31.65%), DRB4 * 01:01:01 (10.50%), and DRB5 * 01:01:01 (10.50%). Higher than expected homozygosity was observed at HLA-B (P = 0.022), DQA1 (P = 0.004), DQB1 (P = 0.023), and DRB1 (P = 0.0006) loci. The allele frequency distribution of this population is very similar to the ones observed in other sub-Saharan populations with the exception of lower frequencies of A * 23 (5.55% versus 11.21%) and DQA1 * 03 (4.79% versus 11.72%), and higher frequencies of DPB1 * 30 (2.26% versus 0.37%) and DRB1 * 11 (21.51% versus 15.89%). The knowledge of the diversity and allele/ phenotype frequencies of the HLA alleles of this east African population, can contribute to the understanding of how host genetic factors influence disease susceptibility and effective anti-retroviral treatment of HIV infections and future vaccine trials.
