Toggle Main Menu Toggle Search

Open Access padlockePrints

Common allelic variants of cytochrome P4503A4 and their prevalence in different populations

Lookup NU author(s): Professor Ann Daly

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


Abstract

Marked interindividual variability in expression of CYP3A4 influences the disposition of many endo- and xenobiotics, including the metabolism of steroids, environmental toxins and therapeutically useful drugs. The present study was designed to determine the genetic basis of CYP3A4 variability. We analysed DNA from 82 individuals with known CYP3A4 phenotype including 53 Caucasians and 21 African-American liver donors, seven individuals who were outliers in CYP3A4 metabolism and five individuals in a family of a poor nifedipine metabolizer. In addition, we analysed DNA from the eight person DNA Polymorphism Discovery Resource subset (Coriell Institute) and 89 individuals representing nine ethnic groups. Five non-synonymous mutations in the coding region of CYP3A4 were observed. CYP3A4* 14 (T44C) in exon 1 resulted in an L15P change; CYP3A4* 15 (G14387A) in exon 6 resulted in a R162Q substitution; CYP3A4* 10 (G14422C) in exon 6 resulted in a D174H substitution; CYP3A4* 16 (Cl 5721 G) in exon 7 resulted in a T185S amino acid substitution; and CYP3A4* 12 (C22002T) in exon 11 resulted in a L373F change in the CYP3A4 protein. An additional six single nucleotide polymorphisms (SNPs) in the 5'-UTR, 13 SNPs in the introns and three SNPs in the 3'-UTR were observed. Extensive population differences were observed in the frequencies of various CYP3A4 alleles. None of the 28 CYP3A4 SNPs identified in CYP3A4 phenotyped persons (most individuals being heterozygous for any CYP3A4 variant) was associated with low hepatic CYP3A4 protein expression or low CYP3A4 activity in vivo.


Publication metadata

Author(s): Daly A; Lamba JK; Lin YS; Thummel K; Watkins PB; Strom S; Zhang J; Schuetz EG

Publication type: Article

Publication status: Published

Journal: Pharmacogenetics

Year: 2002

Volume: 12

Issue: 2

Pages: 121-132

ISSN (print): 1744-6872

ISSN (electronic): 1744-6880

Publisher: Lippincott Williams & Wilkins

URL: http://dx.doi.org/10.1097/00008571-200203000-00006

DOI: 10.1097/00008571-200203000-00006


Altmetrics

Altmetrics provided by Altmetric


Actions

Find at Newcastle University icon    Link to this publication


Share