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<p>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. However, up to 30% of patients do not respond to hydroxyurea, likely due to genetic factors. This study involved 148 individuals with SCD investigated the association of hydroxyurea response with genetic variants across 13 loci associated with HbF synthesis and drug metabolism, focusing on <i>MYB, HBB, HBG1, HBG2, BCL11A, KLF10, HAO2, NOS1, ARG2, SAR1A, CYP2C9</i>, and <i>CYP2E1</i>. Significant associations with hydroxyurea response were identified in <i>CYP2C9, CYP2E1, KLF10, BCL11A, ARG2, HBG1, SAR1A, MYB</i>, and <i>NOS1</i> loci. Furthermore, pathway enrichment and gene-gene interaction analyses provide deeper insights into the genetic mechanisms underlying hydroxyurea treatment response, highlighting potential avenues for personalized therapy in SCD management.</p>

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Exploring pharmacogenetic factors influencing hydroxyurea response in tanzanian sickle cell disease patients: a genomic medicine approach

  • 期刊论文

  • 发表日期：

    2025年4月23日

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  • Siana Nkya,
  • Collin Nzunda,
  • Emmanuel Saukiwa,
  • Frida Kaywanga,
  • Eliud Buchard,
  • David Solomon,
  • Heavenlight Christopher,
  • Doreen Ngowi,
  • Julieth Johansen,
  • Florence Urio,
  • Josephine Mgaya,
  • Christina Kindole,
  • Mbonea Yonazi,
  • Salman Karim,
  • Mohamed Zahir Alimohamed,
  • Raphael Z. Sangeda,
  • Clara Chamba,
  • Collet Dandara,
  • Enrico Novelli,
  • Emile R. Chimusa,
  • Julie Makani

摘要

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. However, up to 30% of patients do not respond to hydroxyurea, likely due to genetic factors. This study involved 148 individuals with SCD investigated the association of hydroxyurea response with genetic variants across 13 loci associated with HbF synthesis and drug metabolism, focusing on MYB, HBB, HBG1, HBG2, BCL11A, KLF10, HAO2, NOS1, ARG2, SAR1A, CYP2C9, and CYP2E1. Significant associations with hydroxyurea response were identified in CYP2C9, CYP2E1, KLF10, BCL11A, ARG2, HBG1, SAR1A, MYB, and NOS1 loci. Furthermore, pathway enrichment and gene-gene interaction analyses provide deeper insights into the genetic mechanisms underlying hydroxyurea treatment response, highlighting potential avenues for personalized therapy in SCD management.