Premium
Correlations of CTLA ‐4 gene polymorphisms and hepatitis C chronic infection
Author(s) -
Danilovic Debora L. S.,
MendesCorrea Maria C.,
Lima Érika U.,
Zambrini Heverton,
K. Barros Raffaelle,
Marui Suemi
Publication year - 2012
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2011.02694.x
Subject(s) - genotype , single nucleotide polymorphism , allele , immunology , biology , hepatitis c virus , ctla 4 , snp , t cell , immune system , gene , medicine , genetics , virus
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 CT 60 CTLA ‐4 single ‐ nucleotide polymorphisms ( SNP s) 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.