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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 DalyORCiD


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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


DOI: 10.1046/j.1365-2125.2003.01798.x

PubMed id: 12814460


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