RESUMEN
The present study aimed to analyse the frequencies of human leukocyte antigen HLA-ABCDQB1 and HLA-DRB1 alleles and haplotypes in a subset of 3,732 Han population from Hubei of China. All samples were typed in the HLA-ABCDQB1 and HLA-DRB1 loci using the sequence-based typing method; subsequently, the HLA polymorphisms were analysed. A total of 47 HLA-A, 89 HLA-B, 43 HLA-C, 49 HLA-DRB1 and 24 HLA-DQB1 alleles were identified in the Hubei Han population. The top three most frequent alleles in the HLA-ABCDQB1 and HLA-DRB1 were A*11:01 (0.2617), A*24:02 (0.1590), A*02:07 (0.1281); B*46:01 (0.1502), B*40:01 (0.1409) and B*58:01 (0.0616); C*01:02 (0.2023), C*07:02 (0.1691) and C*03:04 (0.1175); and DQB1*03:01 (0.2000), DQB1*03:03 (0.1900), DQB1*06:01 (0.1187); DRB1*09:01 (0.1790), DRB1*15:01 (0.1062) and DRB1*12:02 (0.0841), respectively. Meanwhile, the three most frequent two-loci haplotypes were A*02:07-C*01:02 (0.0929), B*46:01-C*01:02 (0.1366) and DQB1*03:03-DRB1*09:01 (0.1766). The three most frequent three-loci haplotypes were A*02:07-B*46:01-C*01:02 (0.0883), B*46:01-DQB1*03:03-DRB1*09:01 (0.0808) and C*01:02-DQB1*03:03-DRB1*09:01 (0.0837). The three most frequent four-loci haplotypes were A*02:07-B*46:01-C*01:02-DQB1*03:03 (0.0494), B*46:01-DRB1*09:01-C*01:02-DQB1*03:03 (0.0729) and A*02:07-B*46:01-DQB1*03:03-DRB1*09:01 (0.0501). The most frequent five-loci haplotype was A*02:07-B*46:01-C*01:02-DQB1*03:03-DRB1*09:01 (0.0487). Heat maps and multiple correspondence analysis based on the frequencies of HLA specificity indicated that the Hubei Han population might be described into Southern Chinese populations. Our results lay a certain foundation for future population studies, disease association studies and donor recruitment strategies.
Asunto(s)
Pueblo Asiatico/genética , Etnicidad/genética , Genes MHC Clase II , Genes MHC Clase I , Antígenos HLA/genética , Cadenas beta de HLA-DQ/genética , Cadenas HLA-DRB1/genética , Haplotipos/genética , Alelos , China , Análisis por Conglomerados , Frecuencia de los Genes , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígenos HLA-C/genética , HumanosRESUMEN
HLA-B*58:118 differs from HLA-B*58:01:01:01 by one nucleotide exchange at position 556(G>A) with an amino exchange.
Asunto(s)
Genes MHC Clase I , Antígenos HLA-B , Alelos , Secuencia de Bases , Antígenos HLA-B/genética , Humanos , Análisis de Secuencia de ADNRESUMEN
HLA-B*40:317 differs from HLA-A*40:06:01:01 by one nucleotide exchange at position 344(G>T) with an amino exchange.
Asunto(s)
Alelos , Antígenos HLA-B/genética , Prueba de Histocompatibilidad , Leucemia/genética , Secuencia de Bases , Niño , Femenino , HumanosRESUMEN
HLA-B*46:01:21 differs from HLA-B*46:01:01 by one nucleotide exchange at position 834(G>A) with no amino exchange.
Asunto(s)
Pueblo Asiatico/genética , Exones/genética , Antígenos HLA-B/genética , Polimorfismo Genético , Alelos , Secuencia de Bases , Humanos , Análisis de Secuencia de ADN , Homología de SecuenciaRESUMEN
The HIV susceptibility and resistance alleles in the HLA genes were determined by investigating the distribution characteristics of the HLA alleles (A, B, and DRB1) in HIV-infected individuals of the Han population in Hubei, and by comparing these alleles with HIV-negative individuals from the same area. A cohort of 424 HIV-1 infected individuals were chosen as study subjects, and 836 HIV-negative healthy subjects from the same area served as the control population. HLA-A, B, and DRB1 allele typing was performed using polymerase chain reaction-sequence-specific oligonucleotide probes (PCR-SSOP) and polymerase chain reaction-sequencing based typing (PCR-SBT) techniques. Arlequin ver3.0 was used to analyze the allele and haplotype frequencies of HLA-A, B, and DRB 1, whereas Epi Info 7 and SPSS18.0 was used to analyze the differences in the HLA alleles between the HIV-1 positive and HIV-1 negative groups. A*02:03, DRB1*01:01, and DRB1*15:01 alleles and their haplotypes as well as the HLA_Bw4-Bw6 hybrid showed a protective effect on HIV-1 infection. After adjusting for confounding factors such as age and sex, multivariate logistic regression analysis revealed that B*15:02G, DRB1*01:01, and DRB1*15:01 subtypes were the resistance genes of HIV-1 infection, while B*13:01 might increase susceptibility to HIV-1 infection. The correlation between A*02:06 and B*15:01G subtypes and HIV-1 susceptibility was independent of the age and sex of the host. This study demonstrated the influence of genetic factors in humans such as HLA polymorphism on individuals to resist HIV-1 infection. Association studies of HLA polymorphism, susceptibility/resistance to HIV-1 infection, and hosts' genetic background are of significant importance for research on HIV-1 pathogenesis and vaccine design.
Asunto(s)
Infecciones por VIH/genética , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Cadenas HLA-DRB1/genética , China/etnología , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Infecciones por VIH/etnología , Humanos , Modelos Logísticos , Masculino , Polimorfismo GenéticoRESUMEN
Liver transplantation has been established as a curative therapy for acute and chronic liver failure, as well as liver-based inherited metabolic diseases. Because of the complexity of organ transplantation and the worldwide shortage of donor organs, hepatocyte transplantation is being developed as a bridging therapy until donor organs become available, or for amelioration of inherited liver-based diseases. The Gunn rat is a molecular and metabolic model of Crigler-Najjar syndrome type 1, which is characterized by lifelong unconjugated hyperbilirubinemia due to the lack of uridinediphosphoglucuronate glucuronosyltransferase-1 (UGT1A1)-mediated bilirubin glucuronidation. Gunn rats are convenient for evaluating the effect of hepatocyte transplantation or gene therapy, because the extent of UGT1A1 replacement can be assessed by serial determination of serum bilirubin levels, and excretion of bilirubin glucuronides in bile provide definitive evidence of the function of the transplanted hepatocytes or the effect of gene therapy. The core techniques involved in hepatocyte transplantation in Gunn rats are discussed in this chapter.
Asunto(s)
Trasplante de Células/métodos , Síndrome de Crigler-Najjar/cirugía , Técnicas de Transferencia de Gen , Hepatocitos/trasplante , Hepatopatías/cirugía , Animales , Bilis/química , Pigmentos Biliares/análisis , Bilirrubina/análogos & derivados , Bilirrubina/sangre , Bilirrubina/metabolismo , Separación Celular/instrumentación , Separación Celular/métodos , Cromatografía Líquida de Alta Presión , Síndrome de Crigler-Najjar/sangre , Modelos Animales de Enfermedad , Femenino , Terapia Genética/métodos , Glucuronosiltransferasa/genética , Glucuronosiltransferasa/metabolismo , Hepatocitos/metabolismo , Heterocigoto , Homocigoto , Humanos , Hiperbilirrubinemia/sangre , Hígado/metabolismo , Hígado/cirugía , Hepatopatías/metabolismo , Pruebas de Función Hepática , Masculino , Ratas , Ratas GunnRESUMEN
The HIV susceptibility and resistance alleles in the HLA genes were determined by investigating the distribution characteristics of the HLA alleles (A,B,and DRB1) in HIV-infected individuals of the Han population in Hubei,and by comparing these alleles with HIV-negative individuals from the same area.A cohort of 424 HIV-1 infected individuals were chosen as study subjects,and 836 HIV-negative healthy subjects from the same area served as the control population.HLA-A,B,and DRB 1 allele typing was performed using polymemse chain reaction-sequence-specific oligonucleotide probes (PCR-SSOP) and polymerase chain reaction-sequencing based typing (PCR-SBT) techniques.Arlequin ver3.0 was used to analyze the allele and haplotype frequencies of HLA-A,B,and DRB l,whereas Epi Info 7 and SPSS18.0 was used to analyze the differences in the HLA alleles between the HIV-1 positive and HIV-1 negative groups.A*02:03,DRB1*01:01,and DRB1*15:01 alleles and their haplotypes as well as the HLA_Bw4-Bw6 hybrid showed a protective effect on HIV-1 infection.After adjusting for confounding factors such as age and sex,multivariate logistic regression analysis revealed that B* 15:02G,DRB 1*01:01,and DRB 1 * 15:01 subtypes were the resistance genes of HIV-1 infection,while B * 13:01 might increase susceptibility to HIV-1 infection.The correlation between A*02:06 and B*15:01G subtypes and HIV-1 susceptibility was independent of the age and sex of the host.This study demonstrated the influence of genetic factors in humans such as HLA polymorphism on individuals to resist HIV-1 infection.Association studies of HLA polymorphism,susceptibility/resistance to HIV-1 infection,and hosts' genetic background are of significant importance for research on HIV-1 pathogenesis and vaccine design.