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Genetic variation in IL28B and spontaneous clearance of hepatitis C virus

Genetic variation in IL28B and spontaneous clearance of hepatitis C virus
Genetic variation in IL28B and spontaneous clearance of hepatitis C virus
Hepatitis C virus (HCV) infection is the most common blood-borne infection in the United States, with estimates of 4 million HCV-infected individuals in the United States and 170 million worldwide. Most (70-80%) HCV infections persist and about 30% of individuals with persistent infection develop chronic liver disease, including cirrhosis and hepatocellular carcinoma. 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. 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-3, was shown to associate strongly with more than a twofold difference in response to HCV drug treatment. 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.
hepatitis c, IL28B gene
0028-0836
798-801
Thomas, David L.
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Thio, Chloe L.
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Martin, Maureen P.
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Qi, Ying
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Ge, Dongliang
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O'Huigin, Colm
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Kidd, Judith
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Kidd, Kenneth
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Khakoo, Salim I.
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Alexander, Graeme
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Goedert, James J.
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Kirk, Gregory D.
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Donfield, Sharyne M.
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Rosen, Hugo R.
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Tobler, Leslie H.
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Busch, Michael P.
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McHutchison, John G.
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Goldstein, David B.
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Carrington, Mary
0fd214c9-4cbc-4719-9d75-9997cd474bd8
Thomas, David L.
e84d3756-82ad-47a9-9f99-5948f3b7e557
Thio, Chloe L.
9bb90dbe-60a7-4574-b16a-33d7a3ecb07b
Martin, Maureen P.
f754a5fa-a475-425b-b0cb-9913a7afab14
Qi, Ying
60497d12-e88c-4c75-9ba5-6dbd34d418e1
Ge, Dongliang
758ffb3a-c20b-458f-b27a-6b209188b772
O'Huigin, Colm
b27e26e7-e437-411f-88b9-2f34d60934e4
Kidd, Judith
5692ee86-26cf-4e44-81f6-cf9358248115
Kidd, Kenneth
07db0af4-bc37-4dbb-b308-59587e745c8d
Khakoo, Salim I.
6c16d2f5-ae80-4d9b-9100-6bfb34ad0273
Alexander, Graeme
d6f9e2a6-e860-4de0-9266-a6b12a1c55e5
Goedert, James J.
d28c5645-6f66-4763-8527-662cde9a8c13
Kirk, Gregory D.
562ddcaa-f2c2-4e06-b87e-08e99b0e1244
Donfield, Sharyne M.
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Rosen, Hugo R.
d18dde61-16ce-4f49-92b5-c81669565676
Tobler, Leslie H.
b4a94393-09b7-4831-87ee-142ac84293f1
Busch, Michael P.
5f2b5b3f-57e9-49f1-9f6b-99858836b26e
McHutchison, John G.
c533e145-da65-46f5-927a-54ee02073b73
Goldstein, David B.
31e8a7ba-4209-4515-b2cb-0611c8d5573e
Carrington, Mary
0fd214c9-4cbc-4719-9d75-9997cd474bd8

Thomas, David L., Thio, Chloe L., Martin, Maureen P., Qi, Ying, Ge, Dongliang, O'Huigin, Colm, Kidd, Judith, Kidd, Kenneth, Khakoo, Salim I., Alexander, Graeme, Goedert, James J., Kirk, Gregory D., Donfield, Sharyne M., Rosen, Hugo R., Tobler, Leslie H., Busch, Michael P., McHutchison, John G., Goldstein, David B. and Carrington, Mary (2009) Genetic variation in IL28B and spontaneous clearance of hepatitis C virus. Nature, 461 (7265), 798-801. (doi:10.1038/nature08463). (PMID:19759533)

Record type: Article

Abstract

Hepatitis C virus (HCV) infection is the most common blood-borne infection in the United States, with estimates of 4 million HCV-infected individuals in the United States and 170 million worldwide. Most (70-80%) HCV infections persist and about 30% of individuals with persistent infection develop chronic liver disease, including cirrhosis and hepatocellular carcinoma. 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. 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-3, was shown to associate strongly with more than a twofold difference in response to HCV drug treatment. 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.

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More information

e-pub ahead of print date: 16 September 2009
Published date: 8 October 2009
Keywords: hepatitis c, IL28B gene
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 336184
URI: http://eprints.soton.ac.uk/id/eprint/336184
ISSN: 0028-0836
PURE UUID: 634439eb-c2d5-4034-a5fd-25d0676dfc97
ORCID for Salim I. Khakoo: ORCID iD orcid.org/0000-0002-4057-9091

Catalogue record

Date deposited: 16 Mar 2012 14:54
Last modified: 15 Mar 2024 03:12

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Contributors

Author: David L. Thomas
Author: Chloe L. Thio
Author: Maureen P. Martin
Author: Ying Qi
Author: Dongliang Ge
Author: Colm O'Huigin
Author: Judith Kidd
Author: Kenneth Kidd
Author: Salim I. Khakoo ORCID iD
Author: Graeme Alexander
Author: James J. Goedert
Author: Gregory D. Kirk
Author: Sharyne M. Donfield
Author: Hugo R. Rosen
Author: Leslie H. Tobler
Author: Michael P. Busch
Author: John G. McHutchison
Author: David B. Goldstein
Author: Mary Carrington

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