Predicted activity of UGT2B7, ABCB1, OPRM1, and COMT using full-gene haplotypes and their association with the CYP2D6-inferred metabolizer phenotype

Show full item record



Permalink

http://hdl.handle.net/10138/300992

Citation

Wendt , F R , Sajantila , A & Budowle , B 2018 , ' Predicted activity of UGT2B7, ABCB1, OPRM1, and COMT using full-gene haplotypes and their association with the CYP2D6-inferred metabolizer phenotype ' , Forensic Science International: Genetics , vol. 33 , pp. 48-58 . https://doi.org/10.1016/j.fsigen.2017.11.012

Title: Predicted activity of UGT2B7, ABCB1, OPRM1, and COMT using full-gene haplotypes and their association with the CYP2D6-inferred metabolizer phenotype
Author: Wendt, Frank R.; Sajantila, Antti; Budowle, Bruce
Contributor: University of Helsinki, Medicum
Date: 2018-03
Language: eng
Number of pages: 11
Belongs to series: Forensic Science International: Genetics
ISSN: 1872-4973
URI: http://hdl.handle.net/10138/300992
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.
Subject: UGT2B7
ABCB1
OPRM1
COMT
CYP2D6
Comprehensive pharmacogenetics
Molecular autopsy
AMINO-ACID SUBSTITUTIONS
INTEGRATIVE GENOMICS VIEWER
O-METHYLTRANSFERASE COMT
AFFECT PROTEIN FUNCTION
JAPANESE POPULATION
HEALTHY-SUBJECTS
CANCER-PATIENTS
CYP2D6 GENE
PAIN RELIEF
POLYMORPHISMS
319 Forensic science and other medical sciences
3111 Biomedicine
1184 Genetics, developmental biology, physiology
Rights:


Files in this item

Total number of downloads: Loading...

Files Size Format View
1_s2.0_S1872497317302600_main.pdf 1.410Mb PDF View/Open

This item appears in the following Collection(s)

Show full item record