title: Correlations of CTLA-4 gene polymorphisms and hepatitis C chronic infection.
abstract: BACKGROUND
  Cytotoxic T lymphocyte-associated factor 4 (CTLA-4) functions as a negative regulator of T cell-mediated immune response. Molecular changes associated to CTLA-4 gene polymorphisms could reduce its ability to suppress and control lymphocyte proliferation.
  
  
  OBJECTIVE
  To evaluate the frequency of CTLA-4 gene polymorphisms in chronic hepatitis C virus (HCV) infected patients and correlate to clinical and histological findings.
  
  
  METHODS
  We evaluated 112 HCV-infected subjects prospectively selected and 183 healthy controls. Clinical and liver histological data were analysed. -318C > T, A49G and CT60 CTLA-4 single-nucleotide polymorphisms (SNPs) were studied by PCR-RFLP and AT(n) polymorphism by DNA fragment analysis by capillary electrophoresis in automatic sequencer.
  
  
  RESULTS
  Eight AT repetitions in 3'UTR region were more frequent in HCV-infected subjects. We found a positive association of -318C and + 49G with HCV genotype 3 (P = 0.008, OR 9.13, P = 0.004, OR 2.49 respectively) and an inverse association of both alleles with HCV genotype 1 (P = 0.020, OR 0.19, P = 0.002, OR 0.38 respectively). Allele + 49G was also associated to aminotransferases quotients > 3 (qALT, P = 0.034, qAST, P = 0.041). Allele G of CT60 SNP was also associated with qAST > 3 (P = 0.012). Increased number of AT repetitions was positively associated to severe necroinflammatory activity scores in liver biopsies (P = 0.045, OR 4.62).
  
  
  CONCLUSIONS
  CTLA-4 gene polymorphisms were associated to HCV-infection. Eight AT repetitions were more prevalent in HCV-infected subjects. -318C and + 49G alleles were associated to genotypes 1 and 3 infections and increased number of AT repetitions in 3'UTR region favoured severe necroinflammatory activity scores in liver biopsies.
authors.affiliation: Unidade de Tireóide - Laboratório de Endocrinologia Celular e Molecular - LIM 25 Disciplina de Endocrinologia da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil. deboraseguro@hotmail.com
authors.forename: Debora L S
authors.initials: DL
authors.lastname: Danilovic
authors.forename: Maria C
authors.initials: MC
authors.lastname: Mendes-Correa
authors.forename: Erika U
authors.initials: EU
authors.lastname: Lima
authors.forename: Heverton
authors.initials: H
authors.lastname: Zambrini
authors.forename: Raffaelle
authors.initials: R
authors.lastname: K Barros
authors.forename: Suemi
authors.initials: S
authors.lastname: Marui
mesh_terms: D060908:CTLA-4 Antigen / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human