PubMed ID:
19387461
Public Release Type:
Journal
Publication Year: 2009
Affiliation: Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA 15261, USA. YeeL@edc.pitt.edu
DOI:
https://doi.org/10.1038/gene.2009.26
Authors:
Hoofnagle JH,
Fontana RJ,
Wang D,
Kleiner DE,
Terrault N,
Seeff LB,
Zacks S,
Afdhal N,
Agudelo E,
Baker SM,
Belle SH,
Bilonick RA,
Block G,
Borg B,
Brown RS Jr,
Brown S,
Burton JR,
Callison K,
Cannon N,
Cline J,
Conjeevaram HS,
Davis P,
DeMedina M,
Di Bisceglie A,
Donlin M,
Doo E,
Dougherty K,
Dove L,
Everhart J,
Ferris M,
Fried MW,
Geahigan T,
Haritos M,
Harsh D,
Hermitt C,
Hinds M,
Howell CD,
Im K,
Im K,
Jeffers LJ,
Kelley S,
Kelsey S,
Klarquist J,
Koozer L,
Lawlor S,
Liang TJ,
Liang TJ,
Robuck P,
Rosen HR,
Sanda C,
Schaley J,
Shrestha R,
Smith SR,
Stovel S,
Straley S,
Tang G,
Tavis JE,
Taylor MW,
Theodore D,
Thomas SB,
Virahep-C Study,
Wahed A,
Wang P,
Wei Y,
Weston S,
Wiley TE,
Williams M,
Yang H,
Yang H,
Yao E,
Yee LJ,
Yee LJ
Studies:
Viral Resistance to Antiviral Therapy of Chronic Hepatitis C
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.