IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy.
Hepatitis C virus (HCV) infects 3% of the world's population. Treatment of chronic HCV consists of a combination of PEGylated interferon-alpha (PEG-IFN-alpha) and ribavirin (RBV). To identify genetic variants associated with HCV treatment response, we conducted a genome-wide association study of sustained virological response (SVR) to PEG-IFN-alpha/RBV combination therapy in 293 Australian individuals with genotype 1 chronic hepatitis C, with validation in an independent replication cohort consisting of 555 individuals. We report an association to SVR within the gene region encoding interleukin 28B (IL28B, also called IFNlambda3; rs8099917 combined P = 9.25 x 10(-9), OR = 1.98, 95% CI = 1.57-2.52). IL28B contributes to viral resistance and is known to be upregulated by interferons and by RNA virus infection. These data suggest that host genetics may be useful for the prediction of drug response, and they also support the investigation of the role of IL28B in the treatment of HCV and in other diseases treated with IFN-alpha.
Suppiah
Vijayaprakash
V
Storr Liver Unit, University of Sydney, Sydney, Australia.
Moldovan
Max
M
Ahlenstiel
Golo
G
Berg
Thomas
T
Weltman
Martin
M
Abate
Maria Lorena
ML
Bassendine
Margaret
M
Spengler
Ulrich
U
Dore
Gregory J
GJ
Powell
Elizabeth
E
Riordan
Stephen
S
Sheridan
David
D
Smedile
Antonina
A
Fragomeli
Vincenzo
V
Müller
Tobias
T
Bahlo
Melanie
M
Stewart
Graeme J
GJ
Booth
David R
DR
George
Jacob
J
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D001315:Australia; D004359:Drug Therapy, Combination; D005260:Female; D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D012254:Ribavirin / Q000627:therapeutic use*; D016896:Treatment Outcome; D000095022:Interferon Lambda
D000998:Antiviral Agents; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda