2026-08-29T14:55:20Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/175052024-11-29T16:58:53Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Apellániz-Ruiz, M author Inglada-Pérez, L author Naranjo, M E G author Sánchez, L author Mancikova, V author Currás-Freixes, M author de Cubas, A A author Comino-Méndez, I author Triki, S author Rebai, A author Rasool, M author Moya, G author Grazina, M author Opocher, G author Cascón, A author Taboada-Echalar, P author Ingelman-Sundberg, M author Carracedo, A author Robledo Batanero, Mercedes author Llerena, A author Rodriguez Antona, Cristina author 2015-06 Cytochrome 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. Pharmacogenomics J . 2015 ;15(3):288-92 10.1038/tpj.2014.67 1473-1150 The pharmacogenomics journal 25348618 http://hdl.handle.net/20.500.12105/17505 High frequency and founder effect of the CYP3A4*20 loss-of-function allele in the Spanish population classifies CYP3A4 as a polymorphic enzyme.