Toggle Main Menu Toggle Search

Open Access padlockePrints

CYP3A5 phenotype-genotype correlations in a British population

Lookup NU author(s): Dr Barry King, Julian Leathart, Dr Elaine Mutch, Professor Faith Williams, Professor Ann Daly

Downloads

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


Abstract

Aims: To develop a polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP)-based assay to genotype for hepatic CYP3A5 expression and to use this assay to study a British population. Methods: CYP3AS-specific PCR primers were designed with one including a base-pair mismatch to create a RsaI site in samples positive for A6986 (CYP3A5*1 allele). Following PCR and RsaI digestion, different band patterns on electrophoresis were predicted for individuals positive for CYP3A5 (CYP3A5*1 allele) compared with those who do not express the gene (CYP3A5*3 homozygotes). The assay was validated by DNA sequencing. DNA samples from a human liver bank consisting of 22 livers whose CYP3A5 expression had been determined by immunoblotting and a group of random individuals (n = 100) from the North-east of England were genotyped by the new assay. Results: In the liver bank, five out of 22 samples expressed CYP3A5 at significant levels (>20 pmol mg-1 protein) and were found to have the genotype CYP3A5*1/CYP3A5z.ast;3 by the PCR-RFLP assay. All other liver DNA samples were CYP3A5*3 homozygotes. In the group of 100 random individuals, 13 had the genotype CYP3A5*1/CYP3A5*3 and all others were CYP3A5*3 homozygotes, predicting that 13% (95% confidence interval (CI) 6%, 20%) would show significant hepatic CYP3A5 expression. The frequency for the CYP3A5*1 allele was 0.065 (95% CI 0.032, 0.097). Conclusions: We have developed a simple assay for the detection of the CYP3A5*1/CYP3A5*3 alleles and shown that in a British population their frequency is similar to that reported previously. We have also shown a good correlation between hepatic CYP3A5 expression and genotype for a British Caucasian liver bank.


Publication metadata

Author(s): King BP, Leathart JBS, Mutch E, Williams FM, Daly AK

Publication type: Article

Publication status: Published

Journal: British Journal of Clinical Pharmacology

Year: 2003

Volume: 55

Issue: 6

Pages: 625-629

ISSN (print): 0306-5251

ISSN (electronic): 1365-2125

Publisher: Wiley-Blackwell Publishing

URL: http://dx.doi.org/10.1046/j.1365-2125.2003.01798.x

DOI: 10.1046/j.1365-2125.2003.01798.x

PubMed id: 12814460


Altmetrics

Altmetrics provided by Altmetric


Actions

Find at Newcastle University icon    Link to this publication


Share