Genetic variation in IL28B and spontaneous clearance of hepatitis C virus

被引:1681
作者
Thomas, David L. [2 ]
Thio, Chloe L. [2 ]
Martin, Maureen P. [1 ,3 ,4 ]
Qi, Ying [1 ,3 ,4 ]
Ge, Dongliang [5 ]
O'hUigin, Colm [1 ,3 ,4 ]
Kidd, Judith [6 ]
Kidd, Kenneth [6 ]
Khakoo, Salim I. [8 ]
Alexander, Graeme [7 ]
Goedert, James J. [9 ]
Kirk, Gregory D. [10 ]
Donfield, Sharyne M. [11 ]
Rosen, Hugo R. [12 ]
Tobler, Leslie H. [13 ]
Busch, Michael P. [14 ]
McHutchison, John G. [15 ]
Goldstein, David B. [5 ]
Carrington, Mary [1 ,3 ,4 ]
机构
[1] NCI Frederick, SAIC Frederick Inc, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD 21702 USA
[2] Johns Hopkins Univ, Div Infect Dis, Baltimore, MD 21205 USA
[3] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA 02114 USA
[4] Harvard Univ, Boston, MA 02114 USA
[5] Duke Univ, Inst Genome Sci & Policy, Ctr Human Genome Variat, Durham, NC 27708 USA
[6] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA
[7] Univ Cambridge, Dept Med, Cambridge CB2 2QQ, England
[8] Univ London Imperial Coll Sci Technol & Med, Div Med, London W2 1NY, England
[9] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA
[10] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA
[11] Rho Inc, Chapel Hill, NC 27517 USA
[12] Univ Colorado, Hlth Sci Ctr, Div Gastroenterol & Hepatol, Aurora, CO 80045 USA
[13] Blood Syst Res Inst, San Francisco, CA 94118 USA
[14] Duke Univ, Duke Clin Res Inst, Durham, NC 27705 USA
[15] Duke Univ, Sch Med, Div Gastroenterol, Durham, NC 27705 USA
基金
美国国家卫生研究院; 英国惠康基金;
关键词
NATURAL-HISTORY; INFECTION; ALPHA-2A; HOST;
D O I
10.1038/nature08463
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Hepatitis C virus (HCV) infection is the most common bloodborne infection in the United States, with estimates of 4 million HCV-infected individuals in the United States and 170 million worldwide(1). Most (70-80%) HCV infections persist and about 30% of individuals with persistent infection develop chronic liver disease, including cirrhosis and hepatocellular carcinoma(2). Epidemiological, viral and host factors have been associated with the differences in HCV clearance or persistence, and studies have demonstrated that a strong host immune response against HCV favours viral clearance(3,4). Thus, variation in genes involved in the immune response may contribute to the ability to clear the virus. In a recent genome-wide association study, a single nucleotide polymorphism (rs12979860) 3 kilobases upstream of the IL28B gene, which encodes the type III interferon IFN-lambda 3, was shown to associate strongly with more than a twofold difference in response to HCV drug treatment(5). To determine the potential effect of rs12979860 variation on outcome to HCV infection in a natural history setting, we genotyped this variant in HCV cohorts comprised of individuals who spontaneously cleared the virus (n = 388) or had persistent infection (n = 620). We show that the C/C genotype strongly enhances resolution of HCV infection among individuals of both European and African ancestry. To our knowledge, this is the strongest and most significant genetic effect associated with natural clearance of HCV, and these results implicate a primary role for IL28B in resolution of HCV infection.
引用
收藏
页码:798 / U52
页数:5
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