Association of single nucleotide polymorphisms in interferon signaling pathway genes and interferon-stimulated genes with the response to interferon therapy for chronic hepatitis C.
OBJECTIVE
Interferon signaling pathway genes (IPGs) and interferon-stimulated genes (ISGs) are associated with the host response to hepatitis C virus (HCV) infection. We studied single nucleotide polymorphisms (SNPs) in IPGs and ISGs for their associations with response to pegylated interferon alpha-2a (Peg-IFN-alpha) plus ribavirin therapy in HCV genotype-1 infected patients.


METHODS
A two-stage study design was used. First, out of 118 SNPs selected, 91 SNPs from 5 IPGs and 12 ISGs were genotyped in a cohort of 374 treatment-naïve HCV patients and assessed for association with sustained virologic response (SVR). Next, 14 potentially functional SNPs from the OASL gene were studied in this cohort.


RESULTS
Three OASL SNPs (rs3213545 and rs1169279 from stage I, and rs2859398 from stage II), were significantly associated with SVR [rs3213545: p=0.03, RR=1.27 (1.03-1.58); rs1169279: p=0.02, RR=1.32 (1.05-1.65) p=0.02; rs2859398: p=0.02, RR=1.29 (1.04-1.61)] after adjusting for other covariates. Further analysis showed that these three SNPs independently associated with SVR. Additionally, a similar trend towards the associations of these three SNPs with SVR was observed in a smaller, independent HCV cohort consisting of subjects from a number of clinical practice settings.


CONCLUSIONS
Our study suggests that OASL variants are involved in the host response to IFN-based therapy in HCV patients.
Su
Xiaowen
X
Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Yee
Leland J
LJ
Im
KyungAh
K
Rhodes
Shannon L
SL
Tang
YongMing
Y
Tong
Xiaomei
X
Howell
Charles
C
Ramcharran
Darmendra
D
Rosen
Hugo R
HR
Taylor
Milton W
MW
Liang
T Jake
TJ
Yang
Huiying
H
D000998:Antiviral Agents / Q000378:metabolism / Q000627:therapeutic use*; D015331:Cohort Studies; D030541:Databases, Genetic; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000378:metabolism / Q000627:therapeutic use*; D007372:Interferons / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000378:metabolism / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D011994:Recombinant Proteins; D012044:Regression Analysis; D012307:Risk Factors; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics*
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D007372:Interferons; C100416:peginterferon alfa-2a