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
目的:研究HLA-C(histocompatibility complex class C)和PDCD1(programmed cell death 1)在银屑病患者骨髓CD34^+细胞中的表达,以揭示银屑病患者造血干细胞的活性。方法:采用免疫磁珠法分离CD34^+细胞,RT-PCR法分别检测HLA-C、PDCD1的m...目的:研究HLA-C(histocompatibility complex class C)和PDCD1(programmed cell death 1)在银屑病患者骨髓CD34^+细胞中的表达,以揭示银屑病患者造血干细胞的活性。方法:采用免疫磁珠法分离CD34^+细胞,RT-PCR法分别检测HLA-C、PDCD1的mRNA表达。结果:银屑病患者骨髓CD34^+细胞HLA-CmRNA表达水平高于正常对照组(P<0.05),PDCD1 mRNA表达在银屑病组与正常对照组间比较无统计学意义(P>0.05),未发现HLA-C mRNA表达水平与银屑病皮损面积和疾病活动性指数(PASI)评分有直线相关性。结论:影响CD34^+细胞发育分化的某些基因在银屑病患者骨髓CD34^+细胞中表达异常,这些基因表达水平的异常可能引起骨髓造血干细胞活性异常,并参与银屑病的发病。展开更多
Background: Although psoriasis vulgaris (PV) is strongly associated with HLA Cw 0602, it has been proposed that the association of Cw 0602 is due to linkage disequilibrium and that other nearby genes are involved in P...Background: Although psoriasis vulgaris (PV) is strongly associated with HLA Cw 0602, it has been proposed that the association of Cw 0602 is due to linkage disequilibrium and that other nearby genes are involved in PV susceptibility The α helix coiled coil rod homologue (HCR) gene, located 110 kb telomeric to the HLA C locus, is presumed to be one of the PV candidate genes Recently, a 10 kb genomic segment, centromeric to HLA C, defined by two new single nucleotide polymorphisms (SNPs) n 7 A and n 9 C, was found to have a stronger association with psoriasis than the HCR gene Until now, no study of the association of the HCR gene, SNPs n 7, and n 9 has been conducted on Chinese patients with psoriasis Objectives: We aimed to determine whether the genetic polymorphisms of the HCR gene, SNPs n 7 A, and n 9 C were associated with an increased risk of psoriasis in Chinese patients Methods: Using direct sequencing of the HCR gene and the genomic region containing SNPs n 7 and n 9, we investigated the HCR gene, SNPs n 7, and n 9 for disease association in 115 Chinese patients with psoriasis and 103 control subjects The HCR SNPs were confirmed by denaturing high performance liquid chromatography Genotyping for HLA Cw 0602 was also carried out using sequence based typing Results: We observed a different allelic distribution between patient and control groups at nucleotide positions 386, 404, 1802 and 2406 of the HCR gene, and SNPs n 7, and n 9 The associations were much stronger in early onset PV patients (for HCR-386 T and HCR-404 T, odds ratio = 5 63, Pc < 0 0001) The HLA Cw 0602 also displayed a similar association with PV (odds ratio = 5 4, Pc < 0 0001) Moreover, SNP n 7 A, SNP n 9 C, Cw 0602, HCR-386 T, HCR-404 T and HCR-1802 T were in linkage disequilibrium with each other Haplotype based association analysis showed SNP n 7 A SNP n 9 C Cw 0602 HCR-386 T HCR-404 THCR-1802 T HCR-2406 G as a major susceptibility haplotype in this Chinese population (for early onset patients, odds ratio = 5 15, Pc < 0 0001) Conclusion展开更多
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.
文摘目的:研究HLA-C(histocompatibility complex class C)和PDCD1(programmed cell death 1)在银屑病患者骨髓CD34^+细胞中的表达,以揭示银屑病患者造血干细胞的活性。方法:采用免疫磁珠法分离CD34^+细胞,RT-PCR法分别检测HLA-C、PDCD1的mRNA表达。结果:银屑病患者骨髓CD34^+细胞HLA-CmRNA表达水平高于正常对照组(P<0.05),PDCD1 mRNA表达在银屑病组与正常对照组间比较无统计学意义(P>0.05),未发现HLA-C mRNA表达水平与银屑病皮损面积和疾病活动性指数(PASI)评分有直线相关性。结论:影响CD34^+细胞发育分化的某些基因在银屑病患者骨髓CD34^+细胞中表达异常,这些基因表达水平的异常可能引起骨髓造血干细胞活性异常,并参与银屑病的发病。
文摘Background: Although psoriasis vulgaris (PV) is strongly associated with HLA Cw 0602, it has been proposed that the association of Cw 0602 is due to linkage disequilibrium and that other nearby genes are involved in PV susceptibility The α helix coiled coil rod homologue (HCR) gene, located 110 kb telomeric to the HLA C locus, is presumed to be one of the PV candidate genes Recently, a 10 kb genomic segment, centromeric to HLA C, defined by two new single nucleotide polymorphisms (SNPs) n 7 A and n 9 C, was found to have a stronger association with psoriasis than the HCR gene Until now, no study of the association of the HCR gene, SNPs n 7, and n 9 has been conducted on Chinese patients with psoriasis Objectives: We aimed to determine whether the genetic polymorphisms of the HCR gene, SNPs n 7 A, and n 9 C were associated with an increased risk of psoriasis in Chinese patients Methods: Using direct sequencing of the HCR gene and the genomic region containing SNPs n 7 and n 9, we investigated the HCR gene, SNPs n 7, and n 9 for disease association in 115 Chinese patients with psoriasis and 103 control subjects The HCR SNPs were confirmed by denaturing high performance liquid chromatography Genotyping for HLA Cw 0602 was also carried out using sequence based typing Results: We observed a different allelic distribution between patient and control groups at nucleotide positions 386, 404, 1802 and 2406 of the HCR gene, and SNPs n 7, and n 9 The associations were much stronger in early onset PV patients (for HCR-386 T and HCR-404 T, odds ratio = 5 63, Pc < 0 0001) The HLA Cw 0602 also displayed a similar association with PV (odds ratio = 5 4, Pc < 0 0001) Moreover, SNP n 7 A, SNP n 9 C, Cw 0602, HCR-386 T, HCR-404 T and HCR-1802 T were in linkage disequilibrium with each other Haplotype based association analysis showed SNP n 7 A SNP n 9 C Cw 0602 HCR-386 T HCR-404 THCR-1802 T HCR-2406 G as a major susceptibility haplotype in this Chinese population (for early onset patients, odds ratio = 5 15, Pc < 0 0001) Conclusion
