Article
Cross-Ancestry Genome-Wide Association Study Defines the Extended CYP2D6 Locus as the Principal Genetic Determinant of Endoxifen Plasma Concentrations.
Clinical pharmacology and therapeutics - 1 Mar 2023
Khor Chiea Chuen, Winter Stefan, Sutiman Natalia, Mürdter Thomas E, Chen Sylvia, Lim Joanne Siok Liu, Li Zheng, Li Jingmei, Sim Kar Seng, Ganchev Boian, Eccles Diana, Eccles Bryony, Tapper William, Zgheib Nathalie K, Tfayli Arafat, Ng Raymond Chee Hui, Yap Yoon Sim, Lim Elaine, Wong Mabel, Wong Nan Soon, Ang Peter Cher Siang, Dent Rebecca, Tremmel Roman, Klein Kathrin, Schaeffeler Elke, Zhou Yitian, Lauschke Volker M, Eichelbaum Michel, Schwab Matthias, Brauch Hiltrud B, Chowbay Balram, Schroth Werner
Abstract excerpt
The therapeutic efficacy of tamoxifen is predominantly mediated by its active metabolites 4-hydroxy-tamoxifen and endoxifen, whose formation is catalyzed by the polymorphic cytochrome P450 2D6 (CYP2D6). Yet, known CYP2D6 polymorphisms only partially determine metabolite concentrations in vivo. We performed the first cross-ancestry genome-wide association study with well-characterized patients of European,...
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