Control of progression towards liver fibrosis and hepatocellular carcinoma by SOCS3 polymorphisms in chronic HCV-infected patients.
Infect Genet Evol
; 66: 1-8, 2018 12.
Article
em En
| MEDLINE
| ID: mdl-30172885
ABSTRACT
BACKGROUND & AIMS:
Chronic Hepatitis C is one of the most important risk factors of liver cirrhosis and hepatocellular carcinoma. Before reaching these ultimate steps, insulin resistance triggered by hepatitis C virus infection is known to participate in the progression of liver disease. The present study aims to investigate the influence of two functional polymorphisms on SOCS3 mRNA expression and on the outcomes of CHC progression in a North African context. PATIENTS &METHODS:
In this case-control study, 601 Moroccan subjects composed of 200 healthy controls, 101 resolvers and 300 patients with persistent HCV infection including 95 mild chronic hepatitis, 131 Advanced Liver Diseases and 74 HCC were enrolled. They were genotyped for the 4874 A/G (rs4969170) and Aâ¯+â¯930-â¯>â¯G (rs4969168) SOCS3 variants using TaqMan SNPs assays. SOCS3 mRNA expression was assessed using Real Time PCR technique.RESULTS:
Logistic regression analysis showed that variation at rs4969168 was associated with spontaneous clearance of HCV (Pâ¯<â¯0.05). In addition, minor allele frequencies were significantly higher in AdLD patients when compared to the mCHC group both for rs4969168 (Pâ¯=â¯7.0 E-04) and rs4969170 (Pâ¯=â¯4.0 E-05). A significant association between haplotype and liver disease progression was also found. Moreover, SOCS3 mRNA was significantly more expressed in peripheral leukocytes from patients with HCC than in those from mCHC. Finally, rs4969170 was significantly associated with LDL-lipoprotein (Pâ¯=â¯0.04), total cholesterol (Pâ¯=â¯5.0 E-04), and higher fasting glucose levels (Pâ¯=â¯0.005) in patients with persistent HCV infection.CONCLUSIONS:
Our results underline the importance of the functional SOCS3 polymorphisms in the modulation of CHC progression and suggest their contribution to HCC development by affecting its mRNA expression and perturbing key metabolic parameters.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
1_ASSA2030
/
2_ODS3
Base de dados:
MEDLINE
Assunto principal:
Polimorfismo Genético
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Carcinoma Hepatocelular
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Hepatite C Crônica
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Predisposição Genética para Doença
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Proteína 3 Supressora da Sinalização de Citocinas
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Cirrose Hepática
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Neoplasias Hepáticas
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Female
/
Humans
/
Male
Idioma:
En
Revista:
Infect Genet Evol
Ano de publicação:
2018
Tipo de documento:
Article