1. Low Molecular Mass Polypeptide 7 Single Nucleotide Polymorphism is Associated with the Progression of Liver Fibrosis in Patients Infected with Hepatitis C Virus Genotype 4
- Author
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El Abd Ys, Abdel Aziz Ao, Abdel Aziz Ms, Moataza H Omran, El Shenawy R, Elsharkawy A, Reham M. Dawood, El Awady Mk, Bader El Din Ng, Moustafa Am, and Marwa K. Ibrahim
- Subjects
Adult ,Liver Cirrhosis ,Male ,0301 basic medicine ,Proteasome Endopeptidase Complex ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Cirrhosis ,Genotype ,Hepatitis C virus ,Single-nucleotide polymorphism ,Hepacivirus ,medicine.disease_cause ,Polymorphism, Single Nucleotide ,Gastroenterology ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Liver disease ,chemistry.chemical_compound ,Fibrosis ,Internal medicine ,Humans ,Medicine ,Aged ,business.industry ,Ribavirin ,Liver Neoplasms ,Hepatitis C, Chronic ,Middle Aged ,medicine.disease ,Virology ,030104 developmental biology ,chemistry ,Hepatocellular carcinoma ,Disease Progression ,Female ,business - Abstract
BACKGROUND The hepatitis C virus (HCV) is a leading cause of liver disease and the consequent complications of cirrhosis. However, there is no precise biomarker to predict the patients at high risk of developing progressive disease. We showed previously the implication of low molecular mass polypeptide-7 (LMP-7) single nucleotide varia- tions in the response to combined pegylated IFN and ribavirin therapy in patients infected with HCV genotype 4. In this study, we examined the possible relationship between LMP-7 genotypes and both the degree of liver fibrosis and the transition from end stage of fibrosis to hepatocellular carcinoma (HCC). METHODS LMP-7 single nucleotide variation at codon 49 (substitution from A to C) was determined using restriction fragment length polymorphism analysis in leucocyte DNA from healthy subjects (n = 36) and HCV-chronically infected patients of genotype 4 either with different grades of liver fibrosis (n = 77) or with hepatocellular carci- noma (n = 25). Chronic HCV-infected patients having liver fibrosis were categorized into two groups based on the degree of fibrosis, early fibrosis (F0-F2, n = 37) and late fibrosis (F3-F4, n = 40). RESULTS Our results demonstrated that patients with the LMP-7 CA/AA genotypes were more likely to have advanced fibrosis scores than those bearing the CC genotype, although LMP-7 polymorphism does not seem to contribute to the progression from the late stage of fibrosis to hepatocellular carcinoma. CONCLUSIONS These results suggest that LMP-7 polymorphism is a candidate prognostic marker in mathematical models designed for predicting the progression of HCV-related liver disease. Nevertheless, the mechanism whereby LMP-7 leads to the progression of liver fibrosis remains to be determined.
- Published
- 2016