SNPs in the promoter region of the osteopontin gene as a marker predicting the efficacy of interferon-based therapies in patients with chronic hepatitis C

Autor: Kenji Fujiwara, Masashi Naito, Atsushi Matsui, Mie Inao, Sumiko Nagoshi, Nobuko Ito, Tohru Egashira, Hashimoto Michie, Satoshi Mochida, Makoto Nagano, Shunji Mishiro
Rok vydání: 2005
Předmět:
Male
Myxovirus Resistance Proteins
Hepacivirus
medicine.disease_cause
Polymerase Chain Reaction
Linkage Disequilibrium
chemistry.chemical_compound
Interferon
Promoter Regions
Genetic
biology
Drug Administration Routes
Gastroenterology
Middle Aged
Treatment Outcome
RNA
Viral
Drug Therapy
Combination
Female
Viral load
medicine.drug
Adult
Proteasome Endopeptidase Complex
medicine.medical_specialty
Combination therapy
Sialoglycoproteins
Hepatitis C virus
Antiviral Agents
Mannose-Binding Lectin
Polymorphism
Single Nucleotide
GTP-Binding Proteins
Multienzyme Complexes
Predictive Value of Tests
Internal medicine
Ribavirin
medicine
Humans
Aged
Retrospective Studies
Hepatitis
DNA
Hepatitis C
Chronic
Hepatology
biology.organism_classification
medicine.disease
chemistry
Immunology
Cancer research
Osteopontin
Interferons
Biomarkers
Follow-Up Studies
Zdroj: Journal of Gastroenterology. 40:381-388
ISSN: 1435-5922
0944-1174
DOI: 10.1007/s00535-005-1558-3
Popis: The T-helper (Th)1 immune reaction is essential for the eradication of hepatitis C virus (HCV) during interferon (IFN) therapy in patients with chronic hepatitis C. Osteopontin is a cytokine crucial for the initiation of the Th1 response. Recently, we identified four single-nucleotide polymorphisms (SNPs) in the promoter region of the osteopontin gene (OPN), at nucleotide (nt) -155, -443, -616, and -1748, and suggested that the SNP at nt -443 was a marker reflecting hepatitis activity in patients with HCV. Therefore, we examined the possibility that SNPs in OPN were also markers predicting the therapeutic efficacy of IFN in patients with chronic hepatitis C. Blood was collected from 77 patients with chronic hepatitis C who had received either IFN monotherapy or IFN-ribavirin combination therapy (IFN-based therapies). SNPs in OPN, MxA, MBL, and LMP7 were analyzed by Invader assay. Promoter SNPs of OPN at nt -155, -616, and -1748 showed linkage disequilibrium at 100% to each other. Sustained virological response (SVR) was observed in 58% of all patients. The SVR rate was higher in patients with the G/G or G/A alleles in the OPN promoter SNP at nt -1748 than in those with A/A (85% vs 45%; P < 0.05). The SVR rate was also higher in patients with T/T at nt -443 than in those with C/C or C/T (86% vs 47%; P < 0.05). Such differences were particularly evident in patients with HCV genotype 1b who had a pretreatment viral load greater than 100 KIU/ml. All the patients who had G/G or G/A at nt -1748 and T/T at nt -443 obtained an SVR. On the other hand, there was no relationship between the efficacy of IFN-based therapies and SNPs in MxA, MBL, and LMP7, which had been shown to have association with the response to IFN monotherapies. SNPs in the promoter region of OPN may be useful as a marker to predict the efficacy of IFN-based therapies in patients with chronic hepatitis C, and further investigation regarding their real significance is warranted in a large series of patients.
Databáze: OpenAIRE
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