Gene polymorphisms predicting response to hydroxyurea treatment in Bahraini patients with sickle cell disease.

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 n = 390 Bahrainis with a history of sickle cell crises. Responders (n = 127; 68%) were patients achieving HbF ≥ 15% along with other improvements. Non-responders (n = 60; 32%) failed to achieve this threshold despite maximum tolerated dose treatment.

Results: Hydroxyurea treated patients had decreased frequency of painful crises and hospitalizations, increased Hb and HbF and decreased sickle cell hemoglobin (HbS), and white blood cells (WBCs). The minor allele frequency of ARG2 (rs10483801), HBS1L-MYB (rs4895441), CYP2C19 (rs4986893) CYP2C19 (rs4244285), and OATP1B3 (rs3711358) gene was significantly higher in non-responders compared to responders. A negative correlation was found between the number of pain crises and hospitalizations per year and HbF%. No significant correlation was reported between the dosage and the number of hospitalizations per year. No significant correlation was found between the duration of treatment and HbF%.

Conclusions: Findings highlight the importance of a personalized treatment approach to maximize the benefits and minimize the side effects of HU, thereby improving clinical outcomes.