Apellániz-Ruiz, MInglada-Pérez, LNaranjo, M E GSánchez, LMancikova, VCurrás-Freixes, Mde Cubas, A AComino-Méndez, ITriki, SRebai, ARasool, MMoya, GGrazina, MOpocher, GCascón, ATaboada-Echalar, PIngelman-Sundberg, MCarracedo, ARobledo Batanero, MercedesLlerena, ARodriguez Antona, Cristina2024-02-062024-02-062015-06Pharmacogenomics J . 2015 ;15(3):288-92http://hdl.handle.net/20.500.12105/17505Cytochrome P450 3A4 (CYP3A4) is a key drug-metabolizing enzyme. Loss-of-function variants have been reported as rare events, and the first demonstration of a CYP3A4 protein lacking functional activity is caused by CYP3A4*20 allele. Here we characterized the world distribution and origin of CYP3A4*20 mutation. CYP3A4*20 was determined in more than 4000 individuals representing different populations, and haplotype analysis was performed using CYP3A polymorphisms and microsatellite markers. CYP3A4*20 allele was present in 1.2% of the Spanish population (up to 3.8% in specific regions), and all CYP3A4*20 carriers had a common haplotype. This is compatible with a Spanish founder effect and classifies CYP3A4 as a polymorphic enzyme. This constitutes the first description of a CYP3A4 loss-of-function variant with high frequency in a population. CYP3A4*20 results together with the key role of CYP3A4 in drug metabolism support screening for rare CYP3A4 functional alleles among subjects with adverse drug events in certain populations.engAMhttp://creativecommons.org/licenses/by-nc-nd/4.0/AllelesCytochrome P-450 CYP3AAttribution-NonCommercial-NoDerivatives 4.0 Internacional2534861815328810.1038/tpj.2014.671473-1150The pharmacogenomics journalopen access