AUTHOR=Yahouédéhou Sètondji Cocou Modeste Alexandre , Neres Joelma Santana dos Santos , da Guarda Caroline Conceição , Carvalho Suellen Pinheiro , Santiago Rayra Pereira , Figueiredo Camylla Vilas Boas , Fiuza Luciana Magalhães , Ndidi Uche Samuel , de Oliveira Rodrigo Mota , Fonseca Cleverson Alves , Nascimento Valma Maria Lopes , Rocha Larissa Carneiro , Adanho Corynne Stéphanie Ahouéfa , da Rocha Tiago Santos Carvalho , Adorno Elisângela Vitória , Goncalves Marilda Souza TITLE=Sickle Cell Anemia: Variants in the CYP2D6, CAT, and SLC14A1 Genes Are Associated With Improved Hydroxyurea Response JOURNAL=Frontiers in Pharmacology VOLUME=11 YEAR=2020 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2020.553064 DOI=10.3389/fphar.2020.553064 ISSN=1663-9812 ABSTRACT=

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.