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Correlations of CTLA-4 gene polymorphisms and hepatitis C chronic infection
Debora L S Danilovic1, Maria C Mendes-Correa, Erika U Lima
1Unidade 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
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.
Insights
Cytotoxic T lymphocyte-associated factor 4 (CTLA-4) gene polymorphisms are linked to hepatitis C virus (HCV) infection. Specific CTLA-4 variants correlate with HCV genotypes and disease severity, including increased liver inflammation.
Area of Science:
- Immunogenetics
- Hepatology
- Molecular Biology
Background:
- Cytotoxic T lymphocyte-associated factor 4 (CTLA-4) is a key negative regulator of T cell immune responses.
- Polymorphisms in the CTLA-4 gene may impact its regulatory function and influence immune-mediated diseases like chronic hepatitis C.
- Understanding these genetic variations is crucial for deciphering disease pathogenesis and progression.
Purpose of the Study:
- To investigate the prevalence of CTLA-4 gene polymorphisms in patients with chronic hepatitis C virus (HCV) infection.
- To correlate these genetic variations with clinical characteristics and histological liver findings in HCV-infected individuals.
Main Methods:
- Prospective evaluation of 112 HCV-infected patients and 183 healthy controls.
- Analysis of clinical and liver biopsy data.
- Genotyping of CTLA-4 single-nucleotide polymorphisms (-318C>T, A49G, CT60) using PCR-RFLP and AT(n) polymorphism via DNA fragment analysis.
Main Results:
- A higher frequency of eight AT repetitions in the 3'UTR region was observed in HCV-infected subjects.
- The -318C and +49G alleles were associated with HCV genotype 3 and inversely with genotype 1.
- +49G and CT60 G alleles correlated with elevated aminotransferase levels.
- An increased number of AT repetitions was linked to severe necroinflammatory activity in liver biopsies.
Conclusions:
- CTLA-4 gene polymorphisms are significantly associated with HCV infection.
- The prevalence of specific CTLA-4 variants differs between HCV genotypes and influences disease activity.
- The number of AT repetitions in the CTLA-4 3'UTR region is a potential biomarker for severe liver inflammation in HCV patients.
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