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Göteborgs universitets publikationer

Core mutations, IL28B polymorphisms and response to peginterferon/ribavirin treatment in Swedish patients with hepatitis C virus genotype 1 infection

Författare och institution:
Erik Alestig (Institutionen för biomedicin, avdelningen för infektionssjukdomar); B. Arnholm (-); Anders Eilard (Institutionen för biomedicin, avdelningen för infektionssjukdomar); Martin Lagging (Institutionen för biomedicin, avdelningen för infektionssjukdomar); Staffan Nilsson (Institutionen för matematiska vetenskaper, matematisk statistik, Chalmers/GU); Gunnar Norkrans (Institutionen för biomedicin, avdelningen för infektionssjukdomar); T. Wahlberg (-); Rune Wejstål (Institutionen för biomedicin, avdelningen för infektionssjukdomar); Johan Westin (Institutionen för biomedicin, avdelningen för infektionssjukdomar); Magnus Lindh (Institutionen för biomedicin, avdelningen för infektionssjukdomar)
Publicerad i:
BMC Infectious Diseases, 11
Artikel, refereegranskad vetenskaplig
Fulltextlänk (lokalt arkiv):
Sammanfattning (abstract):
Background: Patients infected with hepatitis C virus (HCV) genotype 1 respond poorly to standard treatment with 50% or less achieving sustained virologic response. Predicting outcome is essential and could help avoid unnecessary treatment and reduce health cost. Recently, an association of amino acid substitutions in the core region and treatment outcome was observed in Japanese patients. In the present study, the impact of these mutations on response kinetics and treatment outcome was explored in Caucasian patients. Methods: The core region of HCV pre-treatment samples obtained from 50 patients treated with peginterferon/ribavirin in a previous Swedish clinical trial with genotype 1 infection were sequenced. The alleles at rs12979860, a single nucleotide polymorphism (SNP), were assessed in order to identify any co-association with this strong response predictor. Results: No association between treatment response and substitutions of core residue 91 was found. In contrast, substitutions of core residue 70 were observed in 6/21 (29%) non-responders, but only in one of 29 responders (p = 0.03), and were more common in subgenotype 1b (R70Q in 6 of 13 strains) than in 1a (R70P in 1 of 37 strains, p = 0.004). The rs12979860 SNP upstream of the IL28B gene was overall the strongest response predictor (p = 0.0001). Core 70 substitutions were associated with poorer response kinetics in patients carrying the CT genotype at rs12979860. Conclusions: The results indicate that substitutions of core residue 70 are related to treatment response in Caucasian patients with HCV-1b infection, but are of less importance than IL28B polymorphism.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Medicinska grundvetenskaper ->
Mikrobiologi inom det medicinska området
Klinisk medicin
ribavirin combination therapy, amino-acid substitutions, sustained, virological response, plus ribavirin, pegylated interferon, genetic-variation, ns5a region, predictors, clearance, dynamics
Postens nummer:
Posten skapad:
2011-06-30 15:50
Posten ändrad:
2015-01-16 15:12

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