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DNA polymorphisms and response to treatment in patients with chronic hepatitis C: Results from the HALT-C trial

By Richard W. Lambrecht and Herbert L Bonkovsky


Background/Aim 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 IL-10 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 IL-10 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 IL-10 promoter diplotype was associated with SVR

Topics: hepatitis C, chronic/genetics, polymorphism, genetic, interferon-alpha/therapeutic use, gene frequency, Medicine and Health Sciences
Publisher: OpenCommons@UConn
Year: 2008
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