The mutations in ISDR of NS5A gene are not associated with response to interferon treatment in Turkish patients with chronic hepatitis C virus genotype 1b infection.
OBJECTIVE
A significant association between variations in amino acid sequences resides between 2209-2248 nucleotides of HCV non-structural 5A (NS5A) gene, and response to interferon treatment has been proposed. The aim of this study was to determine whether the amino acid sequence changes in ISDR could be correlated to response to alpha interferon treatment in Turkish patients infected with HCV genotypes 1b and 1a.


METHODS
Thirty-nine patients with chronic C virus infection (35 and 4 patients with genotype 1b and 1a, respectively), receiving 3x3-5 MU of interferon a-2b for six months were included in the study. Following PCR amplification of the region from pre-treatment serum samples, the products were directly sequenced. The amino acid sequence of NS5A was compared with the published sequence for HCV-J (AA 2209-2248). Mutant type was defined as three or more amino acid mutations, and intermediate type as 1-3 amino acids in this region. Otherwise, they were defined as the wild type (no amino acid mutations). HCV RNA serum viremia levels were analyzed by branched DNA assay.


RESULTS
Eighteen patients were responders (R; 46%), whereas 21 patients were non-responders (NR; 54%). Amino acid changes in both R and NR groups did not show significant difference. Intermediate or wild type strains were detected in both groups.


CONCLUSIONS
In this study, we could not determine a significant association between number of amino acid changes in NS5A2209-2248 and response to interferon treatment. In the majority of the patients, it seems that amino acid sequences in this region are well conserved.
Aslan
Nuray
N
Institute of Hepatology, School of Medicine, Ankara University, Ankara, Turkey.
Bozdayi
A Mithat
AM
Cetinkaya
Hülya
H
Sarioğlu
Mustafa
M
Türkay
Cansel
C
Bozkaya
Hakan
H
Karayalçin
Selim
S
Yurtaydin
Cihan
C
Uzunalimoğlu
Ozden
O
D000328:Adult; D001483:Base Sequence; D004279:DNA, Viral; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010597:Pharmacogenetics; D011379:Prognosis; D011446:Prospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D016896:Treatment Outcome; D014421:Turkey; D017361:Viral Nonstructural Proteins / Q000235:genetics*; D012324:RNA-Dependent RNA Polymerase
D004279:DNA, Viral; D016898:Interferon-alpha; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase