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Association of IFNL3 and IFNL4 polymorphisms with hepatitis C virus infection in a population from southeastern Brazil

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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.

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Acknowledgments

This work was supported by FAPESP São Paulo Research Foundation (2010/10.549-1).

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Authors and Affiliations

  1. Department of Infectious and Parasitic Diseases, School of Medicine, University of São Paulo, São Paulo, Brazil

    Ana Catharina de Seixas Santos Nastri & Alessandra Yoshino

  2. Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil

    Ana Catharina de Seixas Santos Nastri, Fernanda de Mello Malta, Flair José Carrilho & João Renato Rebello Pinho

  3. Institute of Tropical Medicine, LIM 07, University of São Paulo, Av. Dr. Enéas Carvalho Aguiar, 500, 2nd floor IMT-II, São Paulo, SP, Brazil

    Fernanda de Mello Malta & João Renato Rebello Pinho

  4. Samuel Oschin Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA

    Márcio Augusto Diniz

  5. Laboratory of Immunology, Health Sciences Institutes (ICS), Federal University of Bahia (UFBA), Salvador, Bahia, Brazil

    Kiyoko Abe-Sandes

  6. Department of Medicine, Federal University of Bahia (UFBA), Salvador, Bahia, Brazil

    Sidney Emanuel Batista dos Santos

  7. Human Genetics and Medical laboratory, Federal University of Pará (UFPA), Belém, Pará, Brazil

    André de Castro Lyra

  8. Hospital Israelita Albert Einstein, São Paulo, Brazil

    João Renato Rebello Pinho

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  1. Ana Catharina de Seixas Santos Nastri
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  2. Fernanda de Mello Malta
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Correspondence to Fernanda de Mello Malta.

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This Project was supported by grant 2010/10.549-1 (Fapesp) and the Alves de Queiroz Family Fund for Research. João Renato Rebello Pinho is the recipient of a fellowship from CNPq (Bolsista de Produtividade em Pesquisa do CNPq - Nível 2).

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de Seixas Santos Nastri, A.C., de Mello Malta, F., Diniz, M.A. et al. Association of IFNL3 and IFNL4 polymorphisms with hepatitis C virus infection in a population from southeastern Brazil. Arch Virol 161, 1477–1484 (2016). https://doi.org/10.1007/s00705-016-2809-8

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