Title: Next generation sequencing reveals disparate population frequencies among cytochrome P450 genes: clinical pharmacogenomics of the CYP2 family

Authors: William T. Budd; Greg Meyers; Jeri R. Dilts; Katherine O'Hanlon; John R. Woody; David G. Bostwick; John R. Drury; Thomas Reynolds

Addresses: American International Biotechnology, 601 Biotech Drive, Richmond, VA 23235, USA ' American International Biotechnology, 601 Biotech Drive, Richmond, VA 23235, USA ' American International Biotechnology, 601 Biotech Drive, Richmond, VA 23235, USA ' American International Biotechnology, 601 Biotech Drive, Richmond, VA 23235, USA ' American International Biotechnology, 601 Biotech Drive, Richmond, VA 23235, USA ' American International Biotechnology, 601 Biotech Drive, Richmond, VA 23235, USA ' American International Biotechnology, 601 Biotech Drive, Richmond, VA 23235, USA ' American International Biotechnology, 601 Biotech Drive, Richmond, VA 23235, USA

Abstract: 85% of medications prescribed are metabolised by a CYP450 superfamily member. This family contains SNPs linked to medication response. 30,000 participants were evaluated to determine potential differences in ethnic distributions of nucleotide polymorphisms. Next generation sequencing with the Ion Torrent PGM was used to genotype medication response genes. Variations in these key enzymes were common leading to a variety of responses to medication therapy. Our study showed there exists a large range of genetic variation within/between various ethnic groups. With exception of CYP2C9, the wild type genotype is not most common. Each gene showed a unique pattern of distribution that significantly differed within and across ethnic groups. These findings call into question the concept of a 'normal' patient. Our results highlight the need for and applicability of pharmacogenomic testing. Genetic determination of patient response groups can help tailor therapies and increase the likelihood of success.

Keywords: personalised medicine; clinical pharmacogenomics; translational research; cytochrome P450; NGS; next generation sequencing; precision medicine; ethnic variability; medication metabolism; ion torrent; CYP2D6; VKORC; CYP2C9; CYP2C19; population frequencies; SNPs; single nucleotide polymorphisms; medication response genes; genotyping; medication therapy; genetic variation; ethnic groups; patient response groups.

DOI: 10.1504/IJCBDD.2016.074984

International Journal of Computational Biology and Drug Design, 2016 Vol.9 No.1/2, pp.54 - 86

Published online: 28 Feb 2016 *

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