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IL28B polymorphisms are markers of therapy response and are influenced by genetic ancestry in chronic hepatitis C patients from an admixed population

Authors

  • Lourianne N. Cavalcante,

    1. Department of Medicine, Federal University of Bahia (UFBA), Salvador, Bahia, Brazil
    2. Gastro-Hepatology Service – Hospital São Rafael – Monte Tabor, Salvador, Bahia, Brazil
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  • Kiyoko Abe-Sandes,

    1. Laboratory of Immunology – Health Sciences Institute (ICS), Federal University of Bahia (UFBA), Salvador, Bahia, Brazil
    2. Department of Life Sciences, State University of Bahia (UNEB), Salvador, Bahia, Brazil
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  • Ana Luiza D. Angelo,

    1. Laboratory of Immunology – Health Sciences Institute (ICS), Federal University of Bahia (UFBA), Salvador, Bahia, Brazil
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  • Taisa M. B. Machado,

    1. Laboratory of Immunology – Health Sciences Institute (ICS), Federal University of Bahia (UFBA), Salvador, Bahia, Brazil
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  • Denise C. Lemaire,

    1. Laboratory of Immunology – Health Sciences Institute (ICS), Federal University of Bahia (UFBA), Salvador, Bahia, Brazil
    2. Bahiana School of Medicine and Public Health (EBMSP), Salvador, Bahia, Brazil
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  • Carlos M. C. Mendes,

    1. Fima Lifshitz Research Center, Federal University of Bahia, Bahia, Brazil
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  • João R. Pinho,

    1. Institute of Tropical Medicine – Faculty of Medicine, University of São Paulo, São Paulo, SP, Brazil
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  • Fernanda Malta,

    1. Institute of Tropical Medicine – Faculty of Medicine, University of São Paulo, São Paulo, SP, Brazil
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  • Luiz G.C. Lyra,

    1. Department of Medicine, Federal University of Bahia (UFBA), Salvador, Bahia, Brazil
    2. Gastro-Hepatology Service – Hospital São Rafael – Monte Tabor, Salvador, Bahia, Brazil
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  • André C. Lyra

    Corresponding author
    1. Gastro-Hepatology Service – Hospital São Rafael – Monte Tabor, Salvador, Bahia, Brazil
    • Department of Medicine, Federal University of Bahia (UFBA), Salvador, Bahia, Brazil
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Correspondence

André Castro Lyra, R Sócrates Guanaes Gomes 84/401, Salvador, Bahia, CEP: 40 296 720, Brazil

Tel: 55 71 3351 8097

Fax: 55 71 3281 6855

e-mail: aclyra@live.com

Abstract

Background

IL28B polymorphisms are predictors of therapy response in hepatitis C virus (HCV) patients. We do not know whether they are markers of treatment response in admixed populations or not.

Aims

To determine whether IL28B polymorphisms are predictors of therapy response in patients with HCV from an admixed population and are influenced by genetic ancestry.

Methods

rs12979860 and rs8099917 were genotyped in 222 HCV patients treated with pegylated interferon and ribavirin. Ancestry was determined using genetic markers.

Results

IL28B rs12979860 C/C was associated with sustained virological response (SVR), whereas C/T and T/T were associated with failure to therapy (P = 1.12 × 10−5). IL28B rs8099917 T/T was associated with SVR, and G/G and G/T were associated with nonresponse/relapse (NR/R) (P = 8.00 × 10−3). Among HCV genotype 1 patients with C/C genotype, genomic ancestry did not interfere with therapy response. Among patients with rs12979860 T/T genotype, African genetic contribution was greater in the NR/R group (P = 1.51 × 10−3), whereas Amerindian and European genetic ancestry contribution were higher in the SVR group (P = 3.77 × 10−3 and P = 2.16 × 10−2 respectively). Among HCV type 1 patients with rs8099917 T/T, African genetic contribution was significantly greater in the NR/R group (P = 5.0 × 10−3); Amerindian and European ancestry genetic contribution were greater in the SVR group.

Conclusion

IL28B rs12979860 and rs8099917 polymorphisms were predictors of therapy response in HCV genotypes 1, 2 and 3 subjects from an admixed population. Genomic ancestry did not interfere with response to therapy in patients with rs12979860 C/C, whereas it interfered in patients with C/T and T/T genotypes. Among HCV genotype 1 rs8099917 T/T patients, genomic ancestry interfered with response to therapy.

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