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Background: Hydroxyurea is approved for the treatment of paediatric and adult sickle cell disease patients. It causes the synthesis of foetal haemoglobin and decreases platelets and granulocytes, but with a high interindividual variability, requiring higher dosages and escalating toxicity. Hereditary variables should be investigated to personalise treatment. We evaluated the possible influences of and gene polymorphisms on hydroxyurea pharmacokinetics.
Methods: We conducted a retrospective analysis on 79 treated patients. The polymorphisms of (rs683369 G > C) and (rs9376230 C > A and rs9483947 C > T) were genotyped.
Results: Sub-Saharan patients with the rs683369 GG genotype showed a lower drug half-life, compared to those with the GC genotype. In sub-Saharan paediatric female patients, the rs683369 GG genotype was associated with a lower t1/2 than the GC genotype.
Conclusions: The findings demonstrate for the first time how crucial it is to assess the pharmacogenetics of hydroxyurea by taking into account the two sexes in different groups. Additionally, the data were evaluated with consideration for ethnic groups and individually for adults and children. Pharmacogenetic studies could improve the clinical management of hydroxyurea.
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http://dx.doi.org/10.3390/life15081284 | DOI Listing |
Life (Basel)
August 2025
Clinical Pharmacology, Department of Clinical and Biological Sciences, University of Turin, Orbassano, 10043 Turin, Italy.
Background: Hydroxyurea is approved for the treatment of paediatric and adult sickle cell disease patients. It causes the synthesis of foetal haemoglobin and decreases platelets and granulocytes, but with a high interindividual variability, requiring higher dosages and escalating toxicity. Hereditary variables should be investigated to personalise treatment.
View Article and Find Full Text PDFExpert Rev Hematol
August 2025
Department of Family and Community Medicine, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Bahrain.
Background: This study investigated the association between response to hydroxyurea (HU) treatment and fetal hemoglobin (HbF), and the prevalence of mutations that regulate HbF synthesis, drug transport and biotransformation in sickle cell disease (SCD) patients.
Research Design And Methods: Study included = 390 Bahrainis with a history of sickle cell crises. Responders ( = 127; 68%) were patients achieving HbF ≥ 15% along with other improvements.
Health Sci Rep
July 2025
Department of Medical Laboratory Science, Faculty of Health Science and Technology Ebonyi State University Abakaliki Nigeria.
Background And Aim: The study assessed the polymorphic distribution of H63D rs1799945 of HFE gene and clinico-hematological parameters of SCA patients.
Methods: Sixty sickle cell anemia (SCA) patients and 30 healthy controls without sickle cell disease between the ages of 2-38 years were selected for this case-control study from March to July, 2023 in the Northern Ghana. Ethylenediaminetetraacetic acid (EDTA)-anticoagulated blood samples were used for complete blood count estimation using a 5-part hematology autoanalyzer (URIT-5250 China).
Pharmacogenomics J
April 2025
Department of Haematology and Blood Transfusion,, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.
In sub-Saharan Africa, sickle cell disease (SCD) remains a significant public health challenge. Despite the discovery of SCD over a century ago, progress in developing and accessing effective treatments has been limited. Hydroxyurea is the primary drug used for managing SCD and associated with improving clinical outcomes.
View Article and Find Full Text PDFFront Med (Lausanne)
February 2025
Servicio de Hematología y Hemoterapia, Hospital Clínico San Carlos, Madrid, Spain.
Objective/background: Sickle cell disease (SCD) is a monogenic disease with a highly variable phenotype depending on the amount of fetal hemoglobin (HbF), the main modulator. Variation of HbF levels among patients is genetically regulated. HbF determines both the phenotype of the disease and the response to treatment with the main drug used, hydroxyurea.
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