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

• Published in: Liver international Vol. 32; no. 5; pp. 803 - 808
• Main Authors: Danilovic, Debora L. S., Mendes-Correa, Maria C., Lima, Érika U., Zambrini, Heverton, K. Barros, Raffaelle, Marui, Suemi
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.05.2012
• Subjects: 3' Untranslated regions; Biopsy; capillary electrophoresis; Chronic infection; CTLA-4; CTLA-4 Antigen - genetics; CTLA-4 protein; Cytotoxicity; Data processing; Female; Gene polymorphism; Genetic Predisposition to Disease; Genotype; Hepacivirus - genetics; Hepatitis C; Hepatitis C virus; hepatitis C virus genotype; Hepatitis C, Chronic - genetics; Hepatitis C, Chronic - pathology; Humans; Immune response (cell-mediated); Liver; Liver - metabolism; Liver - pathology; Liver - virology; Male; Middle Aged; necroinflammatory activity score; Nucleotide sequence; Polymerase chain reaction; Polymorphism, Single Nucleotide; Promoter Regions, Genetic - genetics; Prospective Studies; Repetition; Restriction fragment length polymorphism; Risk Factors; Single-nucleotide polymorphism
• ISSN: 1478-3223; 1478-3231; 1478-3231
• DOI: 10.1111/j.1478-3231.2011.02694.x

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.