title: Favourable IFNL3 genotypes are associated with spontaneous clearance and are differentially distributed in Aboriginals in Canadian HIV-hepatitis C co-infected individuals.
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.
authors: Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC H3A 1A2, Canada. nasheed.moqueet@mail.mcgill.ca.
authors: Nasheed
authors: N
authors: Moqueet
authors: Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC H3A 1A2, Canada. claire.infante-rivard@mcgill.ca.
authors: Claire
authors: C
authors: Infante-Rivard
authors: Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC H3A 1A2, Canada. robert.platt@mcgill.ca.
authors: Robert W
authors: RW
authors: Platt
authors: Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel 4031, Switzerland. jyoung@uhbs.ch.|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. jyoung@uhbs.ch.
authors: Jim
authors: J
authors: Young
authors: The Ottawa Hospital-Research Institute, Ottawa, ON K1Y 4E9, Canada. ccooper@toh.on.ca.
authors: Curtis
authors: C
authors: Cooper
authors: BC Centre for Excellence in HIV/AIDS, Vancouver, BC V6Z 1Y6, Canada. mhull@cfenet.ubc.ca.
authors: Mark
authors: M
authors: Hull
authors: Toronto General Research Institute, University Health Network, University of Toronto, Toronto, ON M5G 2M9, Canada. sharon.walmsley@uhn.ca.
authors: Sharon
authors: S
authors: Walmsley
authors: Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC H3A 1A2, Canada. marina.klein@mcgill.ca.|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. marina.klein@mcgill.ca.
authors: Marina B
authors: MB
authors: Klein
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D016174:Hepacivirus / Q000472:pathogenicity; D006526:Hepatitis C / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda