Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression

Citation
P. Kuehl et al., Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression, NAT GENET, 27(4), 2001, pp. 383-391
Citations number
44
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
NATURE GENETICS
ISSN journal
1061-4036 → ACNP
Volume
27
Issue
4
Year of publication
2001
Pages
383 - 391
Database
ISI
SICI code
1061-4036(200104)27:4<383:SDICPA>2.0.ZU;2-A
Abstract
Variation in the CYP3A enzymes, which act in drug metabolism, influences ci rculating steroid levels and responses to half of all oxidatively metaboliz ed drugs. CYP3A activity is the sum activity of the family of CYP3A genes, including CYP3A5, which is polymorphically expressed at high levels in a mi nority of Americans of European descent and Europeans thereafter collective ly referred to as 'Caucasians'). Only people with at least one CYP3A5*1 all ele express large amounts of CYP3A5. Our findings show that single-nucleoti de polymorphisms (SNPs) in CYP3A5*3 and CYP3A5*6 that cause alternative spl icing and protein truncation result in the absence of CYP3A5 from tissues o f some people. CYP3A5 was more frequently expressed in livers of African Am ericans (60%) than in those of Caucasians (33%). Because CYP3A5 represents at least 50% of the total hepatic CYP3A content in people polymorphically e xpressing CYP3A5, CYP3A5 may be the most important genetic contributor to i nterindividual and interracial differences in CYP3A-dependent drug clearanc e and in responses to many medicines.