Global genetic variation of select opiate metabolism genes in self-reported healthy individuals

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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.

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