期刊
PHARMACOGENOMICS JOURNAL
卷 15, 期 3, 页码 288-292出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/tpj.2014.67
关键词
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资金
- Spanish Ministry of Economy and Competiveness [SAF2012-35779]
- CIBERER
- Severo Ochoa
- European Union [259735]
- European Union (FSE)
- Gobierno de Extremadura
- Consejeria de Empleo, Empresa e Innovacion Grant [PD10199]
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.
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