title: The HLA-G 14-base pair deletion allele and the deletion/deletion genotype are associated with persistent HBe antigenemia in chronic hepatis B infection.
abstract: OBJECTIVE
  HLA-G has well-recognized immunomodulatory properties, and this molecule is frequently expressed in the livers of hepatitis B virus (HBV)-infected patients. Because the HLA-G 14 bp-insertion/deletion polymorphism (rs371194629) has been associated with the magnitude of HLA-G expression, we evaluated this polymorphism in the recognized evolutionary forms of chronic HBV infection.
  
  
  METHODS
  We studied 196 chronic HBV-infected patients (118 HBeAg-negative chronic hepatitis, 53 HBeAg-positive chronic hepatitis and 25 inactive carriers exhibiting low levels of serum HBVDNA and persistently normal ALT levels), and 202 healthy individuals. Chronic hepatitis HLA-G typing was performed using PCR-amplified DNA hybridized with specific primers.
  
  
  RESULTS
  The frequencies of the insertion/deletion alleles and genotypes were very similar in patients and controls. After patient stratification according to the evolutionary form of the chronic HBV infection, the frequencies of the deletion allele (P=0.0460; OR=1.26; 95%CI=1.01-1.45) and of the deletion/deletion genotype (P=0.0356; OR=2.08; 95%CI=1.05-4.09) were overrepresented in HBeAg-positive patients when compared to HBeAg-negative patients. No differences were observed when HBV inactive carriers were compared to HBeAg-negative chronic hepatitis patients.
  
  
  CONCLUSIONS
  Because the 14-bp deletion allele has been associated with increased HLA-G production and because HLA-G may down regulate the cytotoxic activity of TCD8 and NK cells, patients exhibiting the 14-bp deletion allele at single or double doses are at increased risk for developing chronic forms of HBV associated with persistent viremia and worse prognoses.
authors.affiliation: Division of Gastroenterology, Department of Medicine, Faculty of Medicine of Ribeirão Preto, University of São Paulo (FMRP-USP), Brazil. Electronic address: sandrocferreira@terra.com.br.
authors.forename: Sandro da Costa
authors.initials: SD
authors.lastname: Ferreira
authors.affiliation: Division of Gastroenterology, Department of Medicine, Faculty of Medicine of Ribeirão Preto, University of São Paulo (FMRP-USP), Brazil; Department of Medicine, University Federal of São Carlos (UFSCAR), Brazil.
authors.forename: Silvana Gama Florêncio
authors.initials: SG
authors.lastname: Chachá
authors.affiliation: Division of Gastroenterology, Department of Medicine, Faculty of Medicine of Ribeirão Preto, University of São Paulo (FMRP-USP), Brazil.
authors.forename: Fernanda Fernandes
authors.initials: FF
authors.lastname: Souza
authors.affiliation: Division of Gastroenterology, Department of Medicine, Faculty of Medicine of Ribeirão Preto, University of São Paulo (FMRP-USP), Brazil.
authors.forename: Andreza Corrêa
authors.initials: AC
authors.lastname: Teixeira
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Faculty of Medicine of Ribeirão Preto, University of São Paulo (FMRP-USP), Brazil.
authors.forename: Rodrigo de Carvalho
authors.initials: RC
authors.lastname: Santana
authors.affiliation: Division of Clinical Immunology, Department of Medicine, Faculty of Medicine of Ribeirão Preto, University of São Paulo (FMRP-USP), Brazil.
authors.forename: Neifi Hassan Saloun
authors.initials: NH
authors.lastname: Deghaide
authors.affiliation: Division of Gastroenterology, Department of Medicine, Faculty of Medicine of Ribeirão Preto, University of São Paulo (FMRP-USP), Brazil.
authors.forename: Sandra
authors.initials: S
authors.lastname: Rodrigues
authors.affiliation: Department of Genetics, Faculty of Medicine of Ribeirão Preto, University of São Paulo (FMRP-USP), Brazil.
authors.forename: Leonardo A
authors.initials: LA
authors.lastname: Marano
authors.affiliation: Departamento de Química - Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP - USP), Brazil.
authors.forename: Celso Teixeira
authors.initials: CT
authors.lastname: Mendes-Junior
authors.affiliation: Department of Pathology, Faculty of Medicine of Ribeirão Preto, University of São Paulo (FMRP-USP), Brazil.
authors.forename: Leandra Naira Zambelli
authors.initials: LN
authors.lastname: Ramalho
authors.affiliation: Department of Pathology, Faculty of Medicine of Ribeirão Preto, University of São Paulo (FMRP-USP), Brazil.
authors.forename: Sérgio
authors.initials: S
authors.lastname: Zucoloto
authors.affiliation: Division of Clinical Immunology, Department of Medicine, Faculty of Medicine of Ribeirão Preto, University of São Paulo (FMRP-USP), Brazil.
authors.forename: Eduardo Antônio
authors.initials: EA
authors.lastname: Donadi
authors.affiliation: Division of Gastroenterology, Department of Medicine, Faculty of Medicine of Ribeirão Preto, University of São Paulo (FMRP-USP), Brazil.
authors.forename: Ana de Lourdes Candolo
authors.initials: AL
authors.lastname: Martinelli
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000956:Antigens, Viral / Q000378:metabolism*; D002353:Carrier State; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D005838:Genotype; D059951:HLA-G Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000502:physiology*; D019694:Hepatitis B, Chronic / Q000235:genetics*; D006801:Humans; D054643:INDEL Mutation / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014766:Viremia / Q000235:genetics; D055815:Young Adult
chemical_list: D000956:Antigens, Viral; D059951:HLA-G Antigens
keywords: 14 bp-insertion/deletion (I/D); Chronic hepatitis B; HBeAg-positive; HLA-G