DNA polymorphisms and response to treatment in patients with chronic hepatitis C: results from the HALT-C trial.
OBJECTIVE
Certain host genetic polymorphisms reportedly affect the likelihood of a sustained virological response (SVR) to interferon treatment in subjects infected with hepatitis C virus (HCV). As part of the HALT-C trial we evaluated genetic associations among patients infected with HCV genotype 1 who had failed previous interferon treatment.


METHODS
SVR was determined 24 weeks after completing treatment with pegylated interferon alfa-2a and ribavirin. Eight single nucleotide polymorphisms (SNPs) were selected on the basis of previously reported associations with treatment response. Genotypes were assessed by polymerase chain reaction-based assays. The percentage of patients who achieved SVR was determined for each genotype and for an IL10 promoter diplotype.


RESULTS
Among 637 non-Hispanic Caucasian patients there were no significant associations between genotype for any individual SNP (IL10-1082, IL10-592, TNF-308, TNF-238, TGFB1 codon 25, CCL2-2518, EPHX1 codon 113 and AGT-6) and SVR, but SVR was more common among the patients who were homozygous for the ACC IL10 promoter diplotype (adjusted odds ratio, 3.24; 95% confidence interval, 1.33-7.78; p=0.001).


CONCLUSIONS
Among non-Hispanic Caucasian patients treated with peginterferon and ribavirin after failing previous treatment with interferon, homozygosity for the ACC IL10 promoter diplotype was associated with SVR.
Morgan
Timothy R
TR
Division of Gastroenterology, University of California Irvine, Irvine, CA, USA. timothy.morgan@va.gov
Lambrecht
Richard W
RW
Bonkovsky
Herbert L
HL
Chung
Raymond T
RT
Naishadham
Deepa
D
Sterling
Richard K
RK
Fontana
Robert J
RJ
Lee
William M
WM
Ghany
Marc G
MG
Wright
Elizabeth C
EC
O'Brien
Thomas R
TR
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D006239:Haplotypes; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D016753:Interleukin-10 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011237:Predictive Value of Tests; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use; D016896:Treatment Outcome; D044465:White People / Q000235:genetics
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D016753:Interleukin-10; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a