title: Association of IFNL3 and IFNL4 polymorphisms with hepatitis C virus infection in a population from southeastern Brazil.
abstract: Hepatitis C virus (HCV) infection is a major cause of chronic liver disease and associated complications such as liver cirrhosis and hepatocellular carcinoma (HCC). Viral and host factors are known to be predictors for antiviral therapy. Host factors that are predictors of sustained viral response (SVR) were discovered by genome-wide association studies (GWAS), including single-nucleotide polymorphisms (SNPs) in or near the interferon lambda gene (rs8099917, rs12979860 and rs368234815). The aim of the present study was to verify the genotype frequencies of SNPs rs8099917, rs12979860 and rs368234815 and to evaluate the association between SNPs and the outcome of HCV infection, taking into account the population ancestry. In this study, there was an association of the three polymorphisms with both clinical outcome and response to treatment with PEG-IFN and RBV. The polymorphisms rs12979860 and rs368234815 were associated with increased sensitivity (97.7 %, 95 % CI 87.2-100, and 93.3 %, 95 % CI 81.3-98.3; respectively) and with a greater predictive value of a positive response to treatment. In multivariable analysis adjusted by gender, age and ancestry, the haplotype G/T/ΔG was related to non-response to treatment (OR = 21.09, 95 % CI 5.33-83.51; p < 0.001) and to a higher chance of developing chronic infection (OR = 5.46, 95 % CI 2.06-14.46; p = 0.001) when compared to the haplotype T/C/TT. These findings may help to adjust our treatment policies for HCV infection based on greater certainty in studies with populations with such genetic characteristics, as well as allowing us to get to know the genetic profile of our population for these polymorphisms.
authors.affiliation: Department of Infectious and Parasitic Diseases, School of Medicine, University of São Paulo, São Paulo, Brazil.|Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Ana Catharina
authors.initials: AC
authors.lastname: de Seixas Santos Nastri
authors.affiliation: Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil. femalta@yahoo.com.|Institute of Tropical Medicine, LIM 07, University of São Paulo, Av. Dr. Enéas Carvalho Aguiar, 500, 2nd floor IMT-II, São Paulo, SP, Brazil. femalta@yahoo.com.
authors.forename: Fernanda
authors.initials: F
authors.lastname: de Mello Malta
authors.affiliation: Samuel Oschin Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Márcio Augusto
authors.initials: MA
authors.lastname: Diniz
authors.affiliation: Department of Infectious and Parasitic Diseases, School of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Yoshino
authors.affiliation: Laboratory of Immunology, Health Sciences Institutes (ICS), Federal University of Bahia (UFBA), Salvador, Bahia, Brazil.
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Abe-Sandes
authors.affiliation: Department of Medicine, Federal University of Bahia (UFBA), Salvador, Bahia, Brazil.
authors.forename: Sidney Emanuel Batista
authors.initials: SE
authors.lastname: Dos Santos
authors.affiliation: Human Genetics and Medical laboratory, Federal University of Pará (UFPA), Belém, Pará, Brazil.
authors.forename: André
authors.initials: A
authors.lastname: de Castro Lyra
authors.affiliation: Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Flair José
authors.initials: FJ
authors.lastname: Carrilho
authors.affiliation: Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil.|Institute of Tropical Medicine, LIM 07, University of São Paulo, Av. Dr. Enéas Carvalho Aguiar, 500, 2nd floor IMT-II, São Paulo, SP, Brazil.|Hospital Israelita Albert Einstein, São Paulo, Brazil.
authors.forename: João Renato Rebello
authors.initials: JR
authors.lastname: Pinho
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D001938:Brazil; D005260:Female; D055106:Genome-Wide Association Study; D006239:Haplotypes; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology*; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D016896:Treatment Outcome; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011994:Recombinant Proteins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C579163:IFNL4 protein, human