Association of the IFNL4-ΔG allele with impaired spontaneous clearance of hepatitis C virus

Peter V. Aka; Mark H. Kuniholm; Ruth M. Pfeiffer; Alan S. Wang; Wei Tang; Sabrina Chen; Jacquie Astemborski; Michael Plankey; Maria C. Villacres; Marion G. Peters; Seema Desai; Eric C. Seaberg; Brian R. Edlin; Howard D. Strickler; David L. Thomas; Ludmila Prokunina-Olsson; Gerald B. Sharp; Thomas R. O'Brien

doi:10.1093/infdis/jit433

Association of the IFNL4-ΔG allele with impaired spontaneous clearance of hepatitis C virus

Peter V. Aka, Mark H. Kuniholm, Ruth M. Pfeiffer, Alan S. Wang, Wei Tang, Sabrina Chen, Jacquie Astemborski, Michael Plankey, Maria C. Villacres, Marion G. Peters, Seema Desai, Eric C. Seaberg, Brian R. Edlin, Howard D. Strickler, David L. Thomas, Ludmila Prokunina-Olsson, Gerald B. Sharp, Thomas R. O'Brien

Research output: Contribution to journal › Article › peer-review

Abstract

Interferon lambda 4 protein can be generated in IFNL4-ΔG carriers but not IFNL4-TT homozygotes. We studied 890 anti-hepatitis C virus (HCV)-positive participants in the Women's Interagency HIV Study. Among blacks (n = 555), HCV was more often cleared for those with genotype IFNL4-TT/TT (32.6%; odds ratio [OR], 3.59; P = 3.3 × 10^-5) than IFNL4-TT/ΔG (11.3%; OR, 0.95; P =. 86) or IFNL4-ΔG/ΔG (11.9%; referent). Pooling these data with published results in blacks (n = 1678), ORs were 3.84 (P = 8.6 × 10^-14) for IFNL4-TT/TT and 1.44 (P =. 03) IFNL4-TT/ΔG, and the area under the curve was 0.64 for IFNL4-ΔG genotype and 0.61 for rs12979860 (IL28B). IFNL4-ΔG is strongly associated with impaired spontaneous HCV clearance.

Original language	English (US)
Pages (from-to)	350-354
Number of pages	5
Journal	Journal of Infectious Diseases
Volume	209
Issue number	3
DOIs	https://doi.org/10.1093/infdis/jit433
State	Published - Jan 24 2014

Keywords

HCV
IFNL4
IL28B
genetic
viral clearance

ASJC Scopus subject areas

Immunology and Allergy
Infectious Diseases

Access to Document

10.1093/infdis/jit433

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Aka, P. V., Kuniholm, M. H., Pfeiffer, R. M., Wang, A. S., Tang, W., Chen, S., Astemborski, J., Plankey, M., Villacres, M. C., Peters, M. G., Desai, S., Seaberg, E. C., Edlin, B. R., Strickler, H. D., Thomas, D. L., Prokunina-Olsson, L., Sharp, G. B., & O'Brien, T. R. (2014). Association of the IFNL4-ΔG allele with impaired spontaneous clearance of hepatitis C virus. Journal of Infectious Diseases, 209(3), 350-354. https://doi.org/10.1093/infdis/jit433

Association of the IFNL4-ΔG allele with impaired spontaneous clearance of hepatitis C virus. / Aka, Peter V.; Kuniholm, Mark H.; Pfeiffer, Ruth M.; Wang, Alan S.; Tang, Wei; Chen, Sabrina; Astemborski, Jacquie; Plankey, Michael; Villacres, Maria C.; Peters, Marion G.; Desai, Seema; Seaberg, Eric C.; Edlin, Brian R.; Strickler, Howard D.; Thomas, David L.; Prokunina-Olsson, Ludmila; Sharp, Gerald B.; O'Brien, Thomas R.

In: Journal of Infectious Diseases, Vol. 209, No. 3, 24.01.2014, p. 350-354.

Research output: Contribution to journal › Article › peer-review

Aka, PV, Kuniholm, MH, Pfeiffer, RM, Wang, AS, Tang, W, Chen, S, Astemborski, J, Plankey, M, Villacres, MC, Peters, MG, Desai, S, Seaberg, EC, Edlin, BR, Strickler, HD, Thomas, DL, Prokunina-Olsson, L, Sharp, GB & O'Brien, TR 2014, 'Association of the IFNL4-ΔG allele with impaired spontaneous clearance of hepatitis C virus', Journal of Infectious Diseases, vol. 209, no. 3, pp. 350-354. https://doi.org/10.1093/infdis/jit433

Aka, Peter V. ; Kuniholm, Mark H. ; Pfeiffer, Ruth M. ; Wang, Alan S. ; Tang, Wei ; Chen, Sabrina ; Astemborski, Jacquie ; Plankey, Michael ; Villacres, Maria C. ; Peters, Marion G. ; Desai, Seema ; Seaberg, Eric C. ; Edlin, Brian R. ; Strickler, Howard D. ; Thomas, David L. ; Prokunina-Olsson, Ludmila ; Sharp, Gerald B. ; O'Brien, Thomas R. / Association of the IFNL4-ΔG allele with impaired spontaneous clearance of hepatitis C virus. In: Journal of Infectious Diseases. 2014 ; Vol. 209, No. 3. pp. 350-354.

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abstract = "Interferon lambda 4 protein can be generated in IFNL4-ΔG carriers but not IFNL4-TT homozygotes. We studied 890 anti-hepatitis C virus (HCV)-positive participants in the Women's Interagency HIV Study. Among blacks (n = 555), HCV was more often cleared for those with genotype IFNL4-TT/TT (32.6%; odds ratio [OR], 3.59; P = 3.3 × 10-5) than IFNL4-TT/ΔG (11.3%; OR, 0.95; P =. 86) or IFNL4-ΔG/ΔG (11.9%; referent). Pooling these data with published results in blacks (n = 1678), ORs were 3.84 (P = 8.6 × 10-14) for IFNL4-TT/TT and 1.44 (P =. 03) IFNL4-TT/ΔG, and the area under the curve was 0.64 for IFNL4-ΔG genotype and 0.61 for rs12979860 (IL28B). IFNL4-ΔG is strongly associated with impaired spontaneous HCV clearance.",

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N2 - Interferon lambda 4 protein can be generated in IFNL4-ΔG carriers but not IFNL4-TT homozygotes. We studied 890 anti-hepatitis C virus (HCV)-positive participants in the Women's Interagency HIV Study. Among blacks (n = 555), HCV was more often cleared for those with genotype IFNL4-TT/TT (32.6%; odds ratio [OR], 3.59; P = 3.3 × 10-5) than IFNL4-TT/ΔG (11.3%; OR, 0.95; P =. 86) or IFNL4-ΔG/ΔG (11.9%; referent). Pooling these data with published results in blacks (n = 1678), ORs were 3.84 (P = 8.6 × 10-14) for IFNL4-TT/TT and 1.44 (P =. 03) IFNL4-TT/ΔG, and the area under the curve was 0.64 for IFNL4-ΔG genotype and 0.61 for rs12979860 (IL28B). IFNL4-ΔG is strongly associated with impaired spontaneous HCV clearance.

AB - Interferon lambda 4 protein can be generated in IFNL4-ΔG carriers but not IFNL4-TT homozygotes. We studied 890 anti-hepatitis C virus (HCV)-positive participants in the Women's Interagency HIV Study. Among blacks (n = 555), HCV was more often cleared for those with genotype IFNL4-TT/TT (32.6%; odds ratio [OR], 3.59; P = 3.3 × 10-5) than IFNL4-TT/ΔG (11.3%; OR, 0.95; P =. 86) or IFNL4-ΔG/ΔG (11.9%; referent). Pooling these data with published results in blacks (n = 1678), ORs were 3.84 (P = 8.6 × 10-14) for IFNL4-TT/TT and 1.44 (P =. 03) IFNL4-TT/ΔG, and the area under the curve was 0.64 for IFNL4-ΔG genotype and 0.61 for rs12979860 (IL28B). IFNL4-ΔG is strongly associated with impaired spontaneous HCV clearance.

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