TY - JOUR
T1 - Regulatory polymorphisms in the interleukin-18 promoter are associated with hepatitis C virus clearance
AU - An, Ping
AU - Thio, Chloe L.
AU - Kirk, Gregory D.
AU - Donfield, Sharyne
AU - Goedert, James J.
AU - Winkler, Cheryl A.
N1 - Funding Information:
Received 23 January 2008; accepted 14 April 2008; electronically published XX September 2008. Potential conflicts of interest: none reported. Presented in part: 57th Annual Meeting of American Society of Human Genetics, San Diego, 23–27 October 2007 (abstract 2589). Financial support: National Cancer Institute, National Institutes of Health (grants N01-CO-12400 and R01 DA13324). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US government. Reprints or correspondence: Dr. Cheryl Winkler, Bldg. 560, NCI-FCRDC, Frederick, MD 21702 ([email protected]).
PY - 2008/10/15
Y1 - 2008/10/15
N2 - The immune response is critical in determining the outcome of hepatitis C virus (HCV) infection. Interleukin (IL)-18 is a pivotal mediator of the Th1/Th2-driven immune response. Two IL-18 promoter polymorphisms (-607C/A and -137G/C) and their haplotypes were known to affect IL-18 expression. We examined the role played by these polymorphisms in determining HCV clearance or persistence. Genotyping was performed among African American injection drug users with HCV clearance (n = 91) or HCV persistence (n = 182) and among European Americans with hemophilia who were mainly infected through plasma transfusion. Among injection drug users, IL18 -607A (odds ratio [OR], 3.68 [95% confidence interval {CI},1.85-7.34]) and IL18 -137C (OR, 2.33 [95% CI, 1.24-4.36]) were significantly associated with HCV clearance. A haplotype carrying -607A and -137C (OR, 4.53 [95% CI, 1.77-11.6]) was also strongly associated with viral clearance. No association was found among those with hemophilia. These results suggest that IL18 promoter polymorphism may affect the outcome of HCV infection in certain groups.
AB - The immune response is critical in determining the outcome of hepatitis C virus (HCV) infection. Interleukin (IL)-18 is a pivotal mediator of the Th1/Th2-driven immune response. Two IL-18 promoter polymorphisms (-607C/A and -137G/C) and their haplotypes were known to affect IL-18 expression. We examined the role played by these polymorphisms in determining HCV clearance or persistence. Genotyping was performed among African American injection drug users with HCV clearance (n = 91) or HCV persistence (n = 182) and among European Americans with hemophilia who were mainly infected through plasma transfusion. Among injection drug users, IL18 -607A (odds ratio [OR], 3.68 [95% confidence interval {CI},1.85-7.34]) and IL18 -137C (OR, 2.33 [95% CI, 1.24-4.36]) were significantly associated with HCV clearance. A haplotype carrying -607A and -137C (OR, 4.53 [95% CI, 1.77-11.6]) was also strongly associated with viral clearance. No association was found among those with hemophilia. These results suggest that IL18 promoter polymorphism may affect the outcome of HCV infection in certain groups.
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U2 - 10.1086/592047
DO - 10.1086/592047
M3 - Article
C2 - 18781864
AN - SCOPUS:54749149734
SN - 0022-1899
VL - 198
SP - 1159
EP - 1165
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 8
ER -