Dataset Information

Association of the IFNL4-?G Allele With Impaired Spontaneous Clearance of Hepatitis C Virus.

ABSTRACT: Interferon lambda 4 protein can be generated in IFNL4-?G 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/?G (11.3%; OR, 0.95; P = .86) or IFNL4-?G/?G (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/?G, and the area under the curve was 0.64 for IFNL4-?G genotype and 0.61 for rs12979860 (IL28B). IFNL4-?G is strongly associated with impaired spontaneous HCV clearance.

SUBMITTER: Aka PV

PROVIDER: S-EPMC3883162 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Association of the IFNL4-ΔG Allele With Impaired Spontaneous Clearance of Hepatitis C Virus.

Aka Peter V PV Kuniholm Mark H MH Pfeiffer Ruth M RM Wang Alan S AS Tang Wei W Chen Sabrina S Astemborski Jacquie J Plankey Michael M Villacres Maria C MC Peters Marion G MG Desai Seema S Seaberg Eric C EC Edlin Brian R BR Strickler Howard D HD Thomas David L DL Prokunina-Olsson Ludmila L Sharp Gerald B GB O'Brien Thomas R TR

The Journal of infectious diseases 20130815 3

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 ...[more]

PMID: 23956438

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Project description:Background & aimsSpontaneous clearance of hepatitis C virus (HCV) occurs in approximately 30% of infected persons and less often in populations of African ancestry. Variants in major histocompatibility complex (MHC) and in interferon lambda genes are associated with spontaneous HCV clearance, but there have been few studies of these variants in persons of African ancestry. We performed a dense multi-ancestry genome-wide association study of spontaneous clearance of HCV, focusing on individuals of African ancestry.MethodsWe performed genotype analyses of 4423 people from 3 ancestry groups: 2201 persons of African ancestry (445 with HCV clearance and 1756 with HCV persistence), 1739 persons of European ancestry (701 with HCV clearance and 1036 with HCV persistence), and 486 multi-ancestry Hispanic persons (173 with HCV clearance and 313 with HCV persistence). Samples were genotyped using Illumina (San Diego, CA) arrays and statistically imputed to the 1000 Genomes Project. For each ancestry group, the association of single-nucleotide polymorphisms with HCV clearance was tested by log-additive analysis, and then a meta-analysis was performed.ResultsIn the meta-analysis, significant associations with HCV clearance were confirmed at the interferon lambda gene locus IFNL4-IFNL3 (19q13.2) (P = 5.99 × 10-50) and the MHC locus 6p21.32 (P = 1.15 × 10-21). We also associated HCV clearance with polymorphisms in the G-protein-coupled receptor 158 gene (GPR158) at 10p12.1 (P = 1.80 × 10-07). These 3 loci had independent, additive effects of HCV clearance, and account for 6.8% and 5.9% of the variance of HCV clearance in persons of European and African ancestry, respectively. Persons of African or European ancestry carrying all 6 variants were 24-fold and 11-fold, respectively, more likely to clear HCV infection compared with individuals carrying none or 1 of the clearance-associated variants.ConclusionsIn a meta-analysis of data from 3 studies, we found variants in MHC genes, IFNL4-IFNL3, and GPR158 to increase odds of HCV clearance in patients of European and African ancestry. These findings could increase our understanding of immune response to and clearance of HCV infection.

Dataset Information

Association of the IFNL4-?G Allele With Impaired Spontaneous Clearance of Hepatitis C Virus.

Publications

Association of the IFNL4-ΔG Allele With Impaired Spontaneous Clearance of Hepatitis C Virus.

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