Correlations of CTLA-4 gene polymorphisms and hepatitis C chronic infection

Author(s)

Danilovic, Debora L. S. ^[1] ; Mendes-Correa, Maria C. ^[2] ; Lima, Erika U. ^[1] ; Zambrini, Heverton ^[2] ; Barros, Raffaelle K. ^[3] ; Marui, Suemi ^[1]

Affiliation

^[1] Univ Sao Paulo, Fac Med, Lab Endocrinol Celular & Mol LIM 25, Unidade Tireoide, Disciplina Endocrinol, BR-01246903 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Fac Med, Hosp Clin, Disciplina Molestias Infecciosas, BR-01246903 Sao Paulo - Brazil

^[3] Hosp Servidor Publ Estadual, Serv Endocrinol, Sao Paulo - Brazil

• Document type: Journal article
• Source: LIVER INTERNATIONAL; v. 32, n. 5, p. 803-808, MAY 2012.
• Web of Science Citations: 18

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. 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 HCVinfection. 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. (AU)

• FAPESP's process: 06/06080-2 - Thyroid evaluation in patients with hepatitis C infection: correlation to CTLA-4 gene polymorphisms
• Grantee: Suemi Marui
• Support Opportunities: Regular Research Grants