title: Global genetic variation of select opiate metabolism genes in self-reported healthy individuals.
abstract: CYP2D6 is a key pharmacogene encoding an enzyme impacting poor, intermediate, extensive and ultrarapid phase I metabolism of many marketed drugs. The pharmacogenetics of opiate drug metabolism is particularly interesting due to the relatively high incidence of addiction and overdose. Recently, trans-acting opiate metabolism and analgesic response enzymes (UGT2B7, ABCB1, OPRM1 and COMT) have been incorporated into pharmacogenetic studies to generate more comprehensive metabolic profiles of patients. With use of massively parallel sequencing, it is possible to identify additional polymorphisms that fine tune, or redefine, previous pharmacogenetic findings, which typically rely on targeted approaches. The 1000 Genomes Project data were analyzed to describe population genetic variation and statistics for these five genes in self-reported healthy individuals in five global super- and 26 sub-populations. Findings on the variation of these genes in various populations expand baseline understanding of pharmacogenetically relevant polymorphisms for future studies of affected cohorts.
authors.affiliation: Institute for Molecular Medicine, University of North Texas Health Science Center, Fort Worth, TX, USA.
authors.forename: F R
authors.initials: FR
authors.lastname: Wendt
authors.affiliation: Institute for Molecular Medicine, University of North Texas Health Science Center, Fort Worth, TX, USA.
authors.forename: G
authors.initials: G
authors.lastname: Pathak
authors.affiliation: Department of Forensic Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: A
authors.initials: A
authors.lastname: Sajantila
authors.affiliation: Institute for Molecular Medicine, University of North Texas Health Science Center, Fort Worth, TX, USA.
authors.forename: R
authors.initials: R
authors.lastname: Chakraborty
authors.affiliation: Institute for Molecular Medicine, University of North Texas Health Science Center, Fort Worth, TX, USA.|Center for Human Identification, University of North Texas Health Science Center, Fort Worth, TX USA.|Center of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: B
authors.initials: B
authors.lastname: Budowle
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000701:Analgesics, Opioid / Q000378:metabolism*; D002394:Catechol O-Methyltransferase / Q000235:genetics; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D030541:Databases, Genetic / Q000706:statistics & numerical data; D014453:Glucuronosyltransferase / Q000235:genetics; D006801:Humans; D000071184:Pharmacogenomic Variants / Q000235:genetics*; D017450:Receptors, Opioid, mu / Q000235:genetics*; D057566:Self Report
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000701:Analgesics, Opioid; C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu; D019389:Cytochrome P-450 CYP2D6; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase; C491474:UGT2B7 protein, human; D014453:Glucuronosyltransferase