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.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Naito
Masashi
M
Division of Gastroenterology and Hepatology, Internal Medicine, Saitama Medical School, 38 Morohongo, Moroyama-cho, Iruma-gun, Saitama 350-0495, Japan.
Matsui
Atsushi
A
Inao
Mie
M
Nagoshi
Sumiko
S
Nagano
Makoto
M
Ito
Nobuko
N
Egashira
Tohru
T
Hashimoto
Michie
M
Mishiro
Shunji
S
Mochida
Satoshi
S
Fujiwara
Kenji
K
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D004247:DNA / Q000235:genetics*; D004333:Drug Administration Routes; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D019204:GTP-Binding Proteins / Q000097:blood / Q000235:genetics; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007372:Interferons / Q000008:administration & dosage / Q000627:therapeutic use*; D015810:Linkage Disequilibrium; D008297:Male; D037601:Mannose-Binding Lectin / Q000097:blood / Q000235:genetics; D008875:Middle Aged; D009097:Multienzyme Complexes / Q000097:blood / Q000235:genetics; D064547:Myxovirus Resistance Proteins; D053495:Osteopontin; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011237:Predictive Value of Tests; D011401:Promoter Regions, Genetic; D046988:Proteasome Endopeptidase Complex; D012367:RNA, Viral / Q000235:genetics; D012189:Retrospective Studies; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use; D012795:Sialoglycoproteins / Q000097:blood / Q000235:genetics*; D016896:Treatment Outcome
D000998:Antiviral Agents; D015415:Biomarkers; C579071:MX1 protein, human; D037601:Mannose-Binding Lectin; D009097:Multienzyme Complexes; D064547:Myxovirus Resistance Proteins; D012367:RNA, Viral; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D053495:Osteopontin; D012254:Ribavirin; D004247:DNA; D007372:Interferons; C077436:LMP7 protein; D046988:Proteasome Endopeptidase Complex; D019204:GTP-Binding Proteins