title: Interleukin-6 haplotypes and the response to therapy of chronic hepatitis C virus infection.
abstract: Chronic hepatitis C virus (HCV) infection affects nearly 170 million individuals worldwide. Treatment of HCV with pegylated interferon-alpha-2a is successful in eradicating virus from only 30 to 80% of those treated. Interleukin-6 (IL-6) is an important cytokine involved in the immune response to infectious agents and in vitro studies suggest that host genetic variation, particularly haplotypes, may affect IL-6 expression. We examined the contribution of haplotypes in the IL-6 gene on sustained viral response (SVR) to the therapy for chronic HCV infection. We observed the IL-6 T-T-G-G-G-G-C-A-G-A haplotype to be associated with a lower risk of achieving SVR among Caucasian Americans (CAs) ((relative risk) RR=0.80; 95% CI: 0.66-0.98; P=0.0261). Using a sliding window approach, the rs1800797-(G)-rs1800796-(G)-rs1800795-(G) haplotype was associated with a reduced chance of SVR (RR=0.79; 95% CI: 0.66-0.94; P=0.0081), as was the rs1800796-(G)-rs1800795-(G)-rs2069830-(C) haplotype (RR=0.78; 95% CI: 0.66-0.94; P=0.0065) among CAs. Overall, the rs1800797-(G)-rs1800796-(G)-rs1800795-(G) haplotype was independently associated with a reduced chance of SVR (RR=0.78; 95% CI: 0.62-1.0; P=0.0489) after adjustment for potential confounding factors. Our findings further illustrate the complexity of IL-6 genetic regulation and the potential importance of haplotypes on IL-6 expression. Our findings provide additional support for the potential importance of genetic variation in the IL-6 gene and the response to HCV therapy.
authors.affiliation: Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA 15261, USA. YeeL@edc.pitt.edu
authors.forename: L J
authors.initials: LJ
authors.lastname: Yee
authors.forename: K
authors.initials: K
authors.lastname: Im
authors.forename: B
authors.initials: B
authors.lastname: Borg
authors.forename: H
authors.initials: H
authors.lastname: Yang
authors.forename: T J
authors.initials: TJ
authors.lastname: Liang
mesh_terms: D000328:Adult; D000483:Alleles; D015331:Cohort Studies; D005260:Female; D005786:Gene Expression Regulation; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D016174:Hepacivirus / Q000187:drug effects; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011092:Polyethylene Glycols / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011994:Recombinant Proteins
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D015850:Interleukin-6; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a