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Int. J. Mol. Sci. 2015, 16(3), 6496-6512; doi:10.3390/ijms16036496

Favourable IFNL3 Genotypes Are Associated with Spontaneous Clearance and Are Differentially Distributed in Aboriginals in Canadian HIV-Hepatitis C Co-Infected Individuals

1
Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC H3A 1A2, Canada
2
Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel 4031, Switzerland
3
Department of Medicine, Division of Infectious Diseases/Chronic Viral Illness Service, Royal Victoria Hospital, McGill University Health Centre, 3650 Saint-Urbain Street, Montreal, QC H2X 2P4, Canada
4
The Ottawa Hospital—Research Institute, Ottawa, ON K1Y 4E9, Canada
5
BC Centre for Excellence in HIV/AIDS, Vancouver, BC V6Z 1Y6, Canada
6
Toronto General Research Institute, University Health Network, University of Toronto, Toronto, ON M5G 2M9, Canada
7
The Canadian Co-Infection Study Investigators (see Appendix)
*
Author to whom correspondence should be addressed.
Academic Editor: Tatsuo Kanda
Received: 27 January 2015 / Revised: 13 March 2015 / Accepted: 13 March 2015 / Published: 20 March 2015
(This article belongs to the Special Issue Viral Hepatitis Research)
View Full-Text   |   Download PDF [1012 KB, uploaded 20 March 2015]   |  

Abstract

Canadian Aboriginals are reported to clear Hepatitis C (HCV) more frequently. We tested the association of spontaneous clearance and three single nucleotide polymorphisms (SNPs) near the Interferon-lambda 3 (IFNL3) gene (rs12979860, rs8099917, functional variant rs8103142) and compared the SNP frequencies between HIV-HCV co-infected whites and Aboriginals from the Canadian Co-infection Cohort. HCV treatment-naïve individuals with at least two HCV RNA tests were included (n = 538). A spontaneous clearance case was defined as someone with two consecutive HCV RNA-negative tests, at least six months apart. Data were analyzed using Cox proportional hazards adjusted for sex and ethnicity. Advantageous variants and haplotypes were more common in Aboriginals than Caucasians: 57% vs. 46% had the rs12979860 CC genotype, respectively; 58% vs. 48%, rs8103142 TT; 74% vs. 67%, the rs12979860 C allele; and 67% vs. 64% the TCT haplotype with three favourable alleles. The adjusted Hazard Ratios (95% CI) for spontaneous clearance were: rs12979860: 3.80 (2.20, 6.54); rs8099917: 5.14 (2.46, 10.72); and rs8103142: 4.36 (2.49, 7.62). Even after adjusting for rs12979860, Aboriginals and females cleared HCV more often, HR (95% CI) = 1.53 (0.89, 2.61) and 1.42 (0.79, 2.53), respectively. Our results suggest that favourable IFNL3 genotypes are more common among Aboriginals than Caucasians, and may partly explain the higher HCV clearance rates seen among Aboriginals. View Full-Text
Keywords: Aboriginals; genetic factors; Hepatitis C spontaneous clearance; Hepatitis C epidemiology; HIV-hepatitis C co-infection; interferon lambda 3 Aboriginals; genetic factors; Hepatitis C spontaneous clearance; Hepatitis C epidemiology; HIV-hepatitis C co-infection; interferon lambda 3
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Moqueet, N.; Infante-Rivard, C.; Platt, R.W.; Young, J.; Cooper, C.; Hull, M.; Walmsley, S.; Klein, M.B.; Investigators, T.C.-I. Favourable IFNL3 Genotypes Are Associated with Spontaneous Clearance and Are Differentially Distributed in Aboriginals in Canadian HIV-Hepatitis C Co-Infected Individuals. Int. J. Mol. Sci. 2015, 16, 6496-6512.

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