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Control of progression towards liver fibrosis and hepatocellular carcinoma by SOCS3 polymorphisms in chronic HCV-infected patients
- Source :
- Infection, Genetics and Evolution, Infection, Genetics and Evolution, 2018, 66, pp.1-8. ⟨10.1016/j.meegid.2018.08.027⟩, Infection, Genetics and Evolution, Elsevier, 2018, 66, pp.1-8. ⟨10.1016/j.meegid.2018.08.027⟩
- Publication Year :
- 2018
- Publisher :
- HAL CCSD, 2018.
-
Abstract
- 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.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 A + 930- G (rs4969168) SOCS3 variants using TaqMan SNPs assays. SOCS3 mRNA expression was assessed using Real Time PCR technique.Logistic regression analysis showed that variation at rs4969168 was associated with spontaneous clearance of HCV (P 0.05). In addition, minor allele frequencies were significantly higher in AdLD patients when compared to the mCHC group both for rs4969168 (P = 7.0 E-04) and rs4969170 (P = 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 (P = 0.04), total cholesterol (P = 5.0 E-04), and higher fasting glucose levels (P = 0.005) in patients with persistent HCV infection.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.
- Subjects :
- Liver Cirrhosis
Male
0301 basic medicine
Oncology
Cirrhosis
Genetic Linkage
Hepacivirus
medicine.disease_cause
Linkage Disequilibrium
MESH: Genotype
Liver disease
Gene Frequency
MESH: Liver Neoplasms
MESH: Hepacivirus
SOCS3
MESH: Carcinoma, Hepatocellular
MESH: Polymorphism, Single Nucleotide
Liver Neoplasms
MESH: Genetic Predisposition to Disease
Viral Load
MESH: Case-Control Studies
MESH: Gene Expression Regulation
3. Good health
HCV infection
MESH: Hepatitis C, Chronic
Infectious Diseases
Real-time polymerase chain reaction
MESH: Linkage Disequilibrium
MESH: Suppressor of Cytokine Signaling 3 Protein
Hepatocellular carcinoma
Disease Progression
Female
MESH: Disease Progression
MESH: Liver Cirrhosis
MESH: Viral Load
Microbiology (medical)
medicine.medical_specialty
Carcinoma, Hepatocellular
Genotype
Hepatitis C virus
MESH: Genetic Linkage
Single-nucleotide polymorphism
[SDV.CAN]Life Sciences [q-bio]/Cancer
Biology
Polymorphism, Single Nucleotide
Microbiology
03 medical and health sciences
Insulin resistance
[SDV.CAN] Life Sciences [q-bio]/Cancer
Internal medicine
MESH: Polymorphism, Genetic
Genetics
medicine
MESH: Gene Frequency
Humans
Genetic Predisposition to Disease
Polymorphism
Molecular Biology
Alleles
Ecology, Evolution, Behavior and Systematics
Polymorphism, Genetic
MESH: Humans
MESH: Alleles
mRNA expression
Hepatitis C, Chronic
medicine.disease
MESH: Male
030104 developmental biology
Gene Expression Regulation
Suppressor of Cytokine Signaling 3 Protein
Case-Control Studies
MESH: Biomarkers
MESH: Female
Biomarkers
Subjects
Details
- Language :
- English
- ISSN :
- 15671348 and 15677257
- Database :
- OpenAIRE
- Journal :
- Infection, Genetics and Evolution, Infection, Genetics and Evolution, 2018, 66, pp.1-8. ⟨10.1016/j.meegid.2018.08.027⟩, Infection, Genetics and Evolution, Elsevier, 2018, 66, pp.1-8. ⟨10.1016/j.meegid.2018.08.027⟩
- Accession number :
- edsair.doi.dedup.....67affcb7c90c9e10e0e68ad3c6a5fe1f