title: Role of HLA-DP and HLA-DQ on the clearance of hepatitis B virus and the risk of chronic infection in a multiethnic population.
abstract: HBV infection exhibits geographical variation in its distribution in South America. While HBV rates are low in central Argentina, the north-western region exhibits intermediate HBV rates. Unfortunately, the reasons that could explain this difference are still unknown.
  
  
  
  A total of 1440 Argentines were recruited and grouped into HBV patients, HBV-resolved individuals and healthy controls. Genetic ancestry was assessed by analysis of biparental lineages and ancestry autosomal typing. SNPs of HLA-DPA1 (rs3077), HLA-DPB1 (rs9277542), HLA-DQB1 (rs2856718) and HLA-DQB2 (rs7453920) were determined, and HBV genotyping was performed by phylogenetic analysis in HBV patients.
  
  
  
  Native American ancestry prevailed in the north-western region when compared with central Argentina (P<.0001). However, no differences were observed among the three groups of each region. The distribution of HBV genotypes revealed significant differences (P<.0001). Three SNPs (rs3077, rs9277542 and rs7453920) showed a significant association with protection against chronic HBV and viral clearance in both regions. The remaining SNP showed a significant association with susceptibility to chronic HBV. The frequency rates of rs3077-T, related to protection against chronic HBV and viral clearance, were lower in north-western Argentina when compared with central Argentina. The same uneven frequency rates were observed for SNP rs9277542.
  
  
  
  This is the first study addressing the associations between the HLA-DP and HLA-DQ loci and the protection against chronic HBV and viral clearance in a multiethnic South American population. The uneven distribution of HLA-DP and HLA-DQ supports the HBV epidemiological differences observed in these two regions of Argentina with dissimilar ancestry genetic background.
authors.affiliation: Basic Sciences and Experimental Medicine Institute (ICBME), University Institute of the Italian Hospital of Buenos Aires, Buenos Aires, Argentina.|Scientific and Technological Research Council (CONICET), Buenos Aires, Argentina.
authors.forename: Julieta
authors.identifier: 0000-0003-4781-8005
authors.initials: J
authors.lastname: Trinks
authors.affiliation: Department of Hepatic Disease, Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Chiba, Japan.|Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Nao
authors.initials: N
authors.lastname: Nishida
authors.affiliation: Basic Sciences and Experimental Medicine Institute (ICBME), University Institute of the Italian Hospital of Buenos Aires, Buenos Aires, Argentina.
authors.forename: María Laura
authors.initials: ML
authors.lastname: Hulaniuk
authors.affiliation: Scientific and Technological Research Council (CONICET), Buenos Aires, Argentina.|Genetic Fingerprints Unit, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Mariela
authors.initials: M
authors.lastname: Caputo
authors.affiliation: Department of Hepatic Disease, Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Chiba, Japan.
authors.forename: Takayo
authors.initials: T
authors.lastname: Tsuchiura
authors.affiliation: Hepatology Unit, Italian Hospital of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Sebastián
authors.initials: S
authors.lastname: Marciano
authors.affiliation: Hepatology Unit, Italian Hospital of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Leila
authors.initials: L
authors.lastname: Haddad
authors.affiliation: "Hemocentro Buenos Aires" Foundation, Buenos Aires, Argentina.
authors.forename: Jorgelina
authors.initials: J
authors.lastname: Blejer
authors.affiliation: Hemotherapy Unit, "Pablo Soria" Hospital, San Salvador de Jujuy, Argentina.
authors.forename: Sonia
authors.initials: S
authors.lastname: Bartoli
authors.affiliation: Hepatology Unit, "José María Ramos Mejía" General Hospital, Buenos Aires, Argentina.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Ameigeiras
authors.affiliation: Hepatology Unit, "José María Ramos Mejía" General Hospital, Buenos Aires, Argentina.
authors.forename: Silvia E
authors.initials: SE
authors.lastname: Frías
authors.affiliation: Hepatology Unit, "José María Ramos Mejía" General Hospital, Buenos Aires, Argentina.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Vistarini
authors.affiliation: "San Antonio" Hospital, Gualeguay, Argentina.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Heinrich
authors.affiliation: Infectology and Tropical Medicine Unit, "San Roque" Hospital, San Salvador de Jujuy, Argentina.
authors.forename: Carlos
authors.initials: C
authors.lastname: Remondegui
authors.affiliation: Infectology and Tropical Medicine Unit, "San Roque" Hospital, San Salvador de Jujuy, Argentina.
authors.forename: Susana
authors.initials: S
authors.lastname: Ceballos
authors.affiliation: "Nuestra Señora del Rosario" Clinic, San Salvador de Jujuy, Argentina.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Echenique
authors.affiliation: Central Public Health Laboratory, San Salvador de Jujuy, Argentina.
authors.forename: Miguel
authors.initials: M
authors.lastname: Charre Samman
authors.affiliation: Ambulatory Medical Specialities Center (CEMA), Mar del Plata, Argentina.
authors.forename: Claudia
authors.initials: C
authors.lastname: D'Amico
authors.affiliation: Ambulatory Medical Specialities Center (CEMA), Mar del Plata, Argentina.
authors.forename: Amalia
authors.initials: A
authors.lastname: Rojas
authors.affiliation: Center for Medical Education and Clinical Research "Norberto Quirno" (CEMIC), Buenos Aires, Argentina.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Martínez
authors.affiliation: Center for Medical Education and Clinical Research "Norberto Quirno" (CEMIC), Buenos Aires, Argentina.
authors.forename: Ezequiel
authors.initials: E
authors.lastname: Ridruejo
authors.affiliation: "Hemocentro Buenos Aires" Foundation, Buenos Aires, Argentina.
authors.forename: Roberto J
authors.initials: RJ
authors.lastname: Fernández
authors.affiliation: Transfusional Medicine Unit, Italian Hospital of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Leandro
authors.initials: L
authors.lastname: Burgos Pratx
authors.affiliation: Transfusional Medicine Unit, Italian Hospital of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Horacio
authors.initials: H
authors.lastname: Salamone
authors.affiliation: Transfusional Medicine Unit, Italian Hospital of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Félix
authors.initials: F
authors.lastname: Nuñez
authors.affiliation: Hepatology Unit, Italian Hospital of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Omar
authors.initials: O
authors.lastname: Galdame
authors.affiliation: Hepatology Unit, Italian Hospital of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Adrián
authors.initials: A
authors.lastname: Gadano
authors.affiliation: Scientific and Technological Research Council (CONICET), Buenos Aires, Argentina.|Genetic Fingerprints Unit, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Daniel
authors.initials: D
authors.lastname: Corach
authors.affiliation: Department of Hepatic Disease, Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Chiba, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Sugiyama
authors.affiliation: Scientific and Technological Research Council (CONICET), Buenos Aires, Argentina.|Virology Department, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Diego
authors.initials: D
authors.lastname: Flichman
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Katsushi
authors.initials: K
authors.lastname: Tokunaga
authors.affiliation: Department of Hepatic Disease, Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Chiba, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Mizokami
mesh_terms: D000328:Adult; D000368:Aged; D001118:Argentina / Q000453:epidemiology; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics* / Q000276:immunology; D059867:HLA-DP alpha-Chains / Q000235:genetics / Q000276:immunology; D059868:HLA-DP beta-Chains / Q000235:genetics / Q000276:immunology; D006683:HLA-DQ Antigens / Q000235:genetics / Q000276:immunology; D059866:HLA-DQ beta-Chains / Q000235:genetics / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics* / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000208:ethnology / Q000235:genetics* / Q000276:immunology / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D015999:Multivariate Analysis; D016017:Odds Ratio; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D065840:Protective Factors; D012307:Risk Factors
chemical_list: D006680:HLA Antigens; D059867:HLA-DP alpha-Chains; D059868:HLA-DP beta-Chains; C071172:HLA-DPA1 antigen; C071170:HLA-DPB1 antigen; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; C040626:HLA-Dx antigen
keywords: 
  HBV
  ; HLA genes; Native American; genotypes