Highlights
- •Full-gene haplotypes are described for trans-acting tramadol metabolism genes UGT2B7, ABCB1, OPRM1, and COMT.
- •Population genetic summary statistics are reported for 2,504 1000 Genomes Project individuals.
- •Intergenic analyses indicate moderate association between diplotype information at CYP2D6, UGT2B7, ABCB1, OPRM1, and COMT.
- •There is little association between predicted activity of trans-acting enzymes and CYP2D6 metabolism in healthy individuals.
Abstract
The pharmacogene, CYP2D6, is commonly used to infer metabolizer phenotype of many marketed drugs and endogenous
toxins in ante- and post-mortem patients but only represents the efficiency of phase
1 metabolism. Downstream metabolic enzymes encoded by UGT2B7, ABCB1, OPRM1, and COMT also have been implicated in variable individual response to drugs due to their activity
at different stages of the tramadol ADME (absorption, distribution, metabolism, and excretion) process. While commonly studied as single genes using targeted genotyping
approaches, a more comprehensive tramadol metabolism profile has not been evaluated.
1000 Genomes Project data for UGT2B7, ABCB1, OPRM1, and COMT were used to characterize full-gene haplotypes and their effect on protein function
using in-house excel-based workbooks, PopART, and TreeView. Population genetic summary
statistics and intergenic analyses associated these haplotypes with full-gene CYP2D6-inferred metabolizer phenotype. The findings suggest that UGT2B7, ABCB1, OPRM1, and COMT may contribute to predicted metabolizer phenotype as opposed to relying solely on
CYP2D6.
Keywords
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Article info
Publication history
Published online: November 25, 2017
Accepted:
November 22,
2017
Received in revised form:
November 1,
2017
Received:
September 25,
2017
Identification
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