TY - JOUR
T1 - Exploring pharmacogenetic factors influencing hydroxyurea response in tanzanian sickle cell disease patients
T2 - a genomic medicine approach
AU - Nkya, Siana
AU - Nzunda, Collin
AU - Saukiwa, Emmanuel
AU - Kaywanga, Frida
AU - Buchard, Eliud
AU - Solomon, David
AU - Christopher, Heavenlight
AU - Ngowi, Doreen
AU - Johansen, Julieth
AU - Urio, Florence
AU - Mgaya, Josephine
AU - Kindole, Christina
AU - Yonazi, Mbonea
AU - Karim, Salman
AU - Alimohamed, Mohamed Zahir
AU - Sangeda, Raphael Z.
AU - Chamba, Clara
AU - Dandara, Collet
AU - Novelli, Enrico
AU - Chimusa, Emile R.
AU - Makani, Julie
PY - 2025/4/23
Y1 - 2025/4/23
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/105003100091
U2 - 10.1038/s41397-025-00372-3
DO - 10.1038/s41397-025-00372-3
M3 - Article
AN - SCOPUS:105003100091
SN - 1470-269X
VL - 25
JO - Pharmacogenomics Journal
JF - Pharmacogenomics Journal
IS - 3
M1 - 11
ER -