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

Abstract

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. To evaluate the frequency of CTLA-4 gene polymorphisms in chronic hepatitis C virus (HCV) infected patients and correlate to clinical and histological findings. 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. 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). 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.