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Hydroxyurea in the management of sickle cell disease: pharmacogenomics and enzymatic metabolism

The Pharmacogenomics Journal volume 18, pages 730–739 (2018)Cite this article

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Abstract

Hydroxyurea (HU) was approved to be used in the treatment of sickle cell disease (SCD) because of its anti-sickling potential. However, there is variability in HU response among SCD patients and this can be due to physiological, socioeconomic, environmental, metabolic and/or genetic factors. The present review focuses on the latter two. Three quantitative trait loci, HBG2, BCL11A and HMIP, have been suggested as important markers for HU response. Other genes (ASS1, KLF10, HAO2, MAP3K5, PDE7B, TOX, NOS1, NOS2A, FLT1, ARG1, ARG2, UGT1A1, OR51B5/6, SIN3A, SALL2, SAR1A, UTB, OCTN1, CYP2C9, AQP9, MPO, CYP2E1, and GSTT1) have also been considered. Studies implicate catalase, urease, horseradish peroxidase and enzymes of CYP450 family in HU metabolism. However, little is known about these enzymes. Therefore, further studies are needed to elucidate the metabolic pathway of HU, which will facilitate pharmacogenomic studies and help in identification of candidate genes for predicting HU response.

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  1. Laboratório de Investigação em Genética e Hematologia Translacional – LIGHT, Instituto Gonçalo Moniz - IGM/FIOCRUZ, Salvador, Brazil

    Sètondji Cocou Modeste Alexandre Yahouédéhou, Caroline Conceição da Guarda, Uche Samuel Ndidi, Suellen Pinheiro Carvalho, Rayra Pereira Santiago, Milena Magalhães Aleluia, Rodrigo Mota de Oliveira & Marilda de Souza Gonçalves

  2. Laboratório de Pesquisa em Anemia – LPA, Departamento de Análises Clínicas, Faculdade de Farmácia, Universidade Federal da Bahia, Salvador, Brazil

    Sètondji Cocou Modeste Alexandre Yahouédéhou, Elisângela Vitória Adorno, Suellen Pinheiro Carvalho, Rodrigo Mota de Oliveira & Marilda de Souza Gonçalves

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Yahouédéhou, S.C.M.A., Adorno, E.V., da Guarda, C.C. et al. Hydroxyurea in the management of sickle cell disease: pharmacogenomics and enzymatic metabolism. Pharmacogenomics J 18, 730–739 (2018). https://doi.org/10.1038/s41397-018-0045-1

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