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Correlations of CTLA-4 gene polymorphisms and hepatitis C chronic infection.
Danilovic, Debora L S; Mendes-Correa, Maria C; Lima, Erika U; Zambrini, Heverton; K Barros, Raffaelle; Marui, Suemi.
Afiliação
  • Danilovic DL; 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
Liver Int ; 32(5): 803-8, 2012 May.
Article em En | MEDLINE | ID: mdl-22136395
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. AIMS: 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). CONCLUSION: 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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Hepatite C Crônica / Predisposição Genética para Doença / Polimorfismo de Nucleotídeo Único / Antígeno CTLA-4 Tipo de estudo: Etiology_studies / Observational_studies / Risk_factors_studies Limite: Female / Humans / Male / Middle aged Idioma: En Revista: Liver Int Assunto da revista: GASTROENTEROLOGIA Ano de publicação: 2012 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Hepatite C Crônica / Predisposição Genética para Doença / Polimorfismo de Nucleotídeo Único / Antígeno CTLA-4 Tipo de estudo: Etiology_studies / Observational_studies / Risk_factors_studies Limite: Female / Humans / Male / Middle aged Idioma: En Revista: Liver Int Assunto da revista: GASTROENTEROLOGIA Ano de publicação: 2012 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos