Genetic variation in IL28B is associated with chronic hepatitis C and treatment failure: a genome-wide association study.

Détails

ID Serval
serval:BIB_0243EEF97C35
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Genetic variation in IL28B is associated with chronic hepatitis C and treatment failure: a genome-wide association study.
Périodique
Gastroenterology
Auteur(s)
Rauch A., Kutalik Z., Descombes P., Cai T., Di Iulio J., Mueller T., Bochud M., Battegay M., Bernasconi E., Borovicka J., Colombo S., Cerny A., Dufour J.F., Furrer H., Günthard H.F., Heim M., Hirschel B., Malinverni R., Moradpour D., Müllhaupt B., Witteck A., Beckmann J.S., Berg T., Bergmann S., Negro F., Telenti A., Bochud P.Y.
Collaborateur(s)
Swiss Hepatitis C Cohort Study, Swiss HIV Cohort Study
Contributeur(s)
Negro F., Hadengue A., Kaiser L., Rubbia-Brandt L., Moradpour D., Burgisser P., Francioli P., Estoppey-Younes S., Schoni-Affolter F., Rickenbach M., Martinetti G., Cerny A., Masserey Spicher V., Gorgievski M., Dufour JF., Hirsch H., Heim H., Helbling B., Müllhaupt B., Regenass S., Malinverni R., Meyenberger C., Borovicka J., Dollenmaier G., Cathomas G., Battegay M., Bernasconi E., Böni J., Bucher HC., Bürgisser P., Calmy A., Cattacin S., Cavassini M., Dubs R., Egger M., Elzi L., Fischer M., Flepp M., Fontana A., Francioli P., Furrer H., Fux CA., Gorgievski M., Günthard HF., Hirsch HH., Hirschel B., Hösli I., Kahlert C., Kaiser L., Karrer U., Kind C., Klimkait T., Ledergerber B., Martinetti G., Müller N., Nadal D., Paccaud F., Pantaleo G., Rauch A., Regenass S., Rickenbach M., Rudin C., Schmid P., Schultze D., Schöni-Affolter F., Schüpbach J., Speck R., de Tejada BM. , Taffé P., Telenti A., Trkola A., Vernazza P., Weber R., Yerly S.
ISSN
1528-0012 (Electronic)
ISSN-L
0016-5085
Statut éditorial
Publié
Date de publication
2010
Peer-reviewed
Oui
Volume
138
Numéro
4
Pages
1338-45, 1345.e1-7
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
BACKGROUND & AIMS: Hepatitis C virus (HCV) induces chronic infection in 50% to 80% of infected persons; approximately 50% of these do not respond to therapy. We performed a genome-wide association study to screen for host genetic determinants of HCV persistence and response to therapy.
METHODS: The analysis included 1362 individuals: 1015 with chronic hepatitis C and 347 who spontaneously cleared the virus (448 were coinfected with human immunodeficiency virus [HIV]). Responses to pegylated interferon alfa and ribavirin were assessed in 465 individuals. Associations between more than 500,000 single nucleotide polymorphisms (SNPs) and outcomes were assessed by multivariate logistic regression.
RESULTS: Chronic hepatitis C was associated with SNPs in the IL28B locus, which encodes the antiviral cytokine interferon lambda. The rs8099917 minor allele was associated with progression to chronic HCV infection (odds ratio [OR], 2.31; 95% confidence interval [CI], 1.74-3.06; P = 6.07 x 10(-9)). The association was observed in HCV mono-infected (OR, 2.49; 95% CI, 1.64-3.79; P = 1.96 x 10(-5)) and HCV/HIV coinfected individuals (OR, 2.16; 95% CI, 1.47-3.18; P = 8.24 x 10(-5)). rs8099917 was also associated with failure to respond to therapy (OR, 5.19; 95% CI, 2.90-9.30; P = 3.11 x 10(-8)), with the strongest effects in patients with HCV genotype 1 or 4. This risk allele was identified in 24% of individuals with spontaneous HCV clearance, 32% of chronically infected patients who responded to therapy, and 58% who did not respond (P = 3.2 x 10(-10)). Resequencing of IL28B identified distinct haplotypes that were associated with the clinical phenotype.
CONCLUSIONS: The association of the IL28B locus with natural and treatment-associated control of HCV indicates the importance of innate immunity and interferon lambda in the pathogenesis of HCV infection.
Mots-clé
Adult, Aged, Female, Genetic Variation, Genome-Wide Association Study, Genotype, Haplotypes, Hepatitis C, Chronic/drug therapy, Hepatitis C, Chronic/genetics, Humans, Interferon-alpha/administration & dosage, Interleukins/genetics, Male, Middle Aged, Polyethylene Glycols/administration & dosage, Polymorphism, Single Nucleotide, Recombinant Proteins, Ribavirin/administration & dosage, Treatment Failure
Pubmed
Web of science
Création de la notice
21/04/2010 12:08
Dernière modification de la notice
20/08/2019 13:24
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