Frontiers in Pharmacology (Sep 2020)

Sickle Cell Anemia: Variants in the CYP2D6, CAT, and SLC14A1 Genes Are Associated With Improved Hydroxyurea Response

  • Sètondji Cocou Modeste Alexandre Yahouédéhou,
  • Sètondji Cocou Modeste Alexandre Yahouédéhou,
  • Joelma Santana dos Santos Neres,
  • Caroline Conceição da Guarda,
  • Caroline Conceição da Guarda,
  • Suellen Pinheiro Carvalho,
  • Suellen Pinheiro Carvalho,
  • Rayra Pereira Santiago,
  • Rayra Pereira Santiago,
  • Camylla Vilas Boas Figueiredo,
  • Camylla Vilas Boas Figueiredo,
  • Luciana Magalhães Fiuza,
  • Luciana Magalhães Fiuza,
  • Uche Samuel Ndidi,
  • Rodrigo Mota de Oliveira,
  • Rodrigo Mota de Oliveira,
  • Cleverson Alves Fonseca,
  • Valma Maria Lopes Nascimento,
  • Larissa Carneiro Rocha,
  • Corynne Stéphanie Ahouéfa Adanho,
  • Tiago Santos Carvalho da Rocha,
  • Elisângela Vitória Adorno,
  • Marilda Souza Goncalves,
  • Marilda Souza Goncalves

DOI
https://doi.org/10.3389/fphar.2020.553064
Journal volume & issue
Vol. 11

Abstract

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Differences in hydroxyurea response in sickle cell anemia may arise due to a series of factors with genetic factors appearing to be predominant. This study aims to investigate the effects of single nucleotide polymorphisms in genes encoding drug-metabolizing enzymes and solute carriers on hydroxyurea response, in patients with sickle cell anemia. For that purpose, a total number of 90 patients with sickle cell anemia were recruited, 45 were undergoing hydroxyurea treatment, while 45 were not under the treatment. Association analyses were performed between CYP3A4 (rs2740574), CYP2D6 (rs3892097), CAT (rs7943316 and rs1001179), and SLC14A1 (rs2298720) variants and laboratory parameters. According to our findings, patients with hydroxyurea treatment demonstrated higher HbF levels and a significant improvement in hemolytic, hepatic, inflammatory, and lipid parameters in comparison to those without the treatment. We also found significant associations between the CYP2D6 (rs3892097), CAT (rs7943316 and rs1001179), and SLC14A1 (rs2298720) variants and an improvement of the therapeutic effects, specifically the hemolytic, hepatic, inflammatory, lipid, and renal parameters. In conclusion, our results highlight the importance of the investigated variants, and their strong association with hydroxyurea efficacy in patients with sickle cell anemia, which may be considered in the future as genetic markers.

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