PMID: 9164697Mar 1, 1997Paper

CYP2D6-related oxidation polymorphism in a Canadian Inuit population

Canadian Journal of Physiology and Pharmacology
M Jurima-RometS Geertsen

Abstract

The xenobiotic oxidation polymorphism associated with cytochrome P450 2D6 (CYP2D6) was investigated in 152 genetically related and unrelated healthy Inuit subjects living in the High Arctic of eastern Canada. Phenotyping was based on HPLC determination of the CYP2D6-related dextromethorphan metabolic ratio in overnight urine samples after oral administration of 30 mg dextromethorphan hydrobromide. The log metabolic ratio was bimodally distributed, with three subjects classified as poor metabolizers (PMs). In subjects unrelated in the first degree, the incidence of the PM phenotype was 3 of 90 or 3.3%. PCR-based analyses of DNA for variants of the CYP2D6 gene demonstrated that the PMs of dextromethorphan had the defective allele CYP2D6*4. The estimated frequency of the CYP2D6*4 allele was 0.067-0.083, which is lower than the frequency in Caucasians but higher than the frequency in Oriental populations. The CYP2D6*3 and the CYP2D6*6 alleles were not detected in the Inuit population. The CYP2D6*10 allele was present in only four unrelated subjects, classified as extensive metabolizers (EMs), resulting in an estimated allele frequency of 0.022, which is much lower than in Oriental populations. This study demonstrated the existence ...Continue Reading

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Citations

May 12, 2000·Toxicology in Vitro : an International Journal Published in Association with BIBRA·M Jurima-RometM Nowakowska
Mar 7, 2003·Genomics·Benjamin FletcherMark G Thomas
Oct 16, 2014·Expert Opinion on Drug Metabolism & Toxicology·Adrián LLerenaEduardo Tarazona-Santos
Feb 2, 2018·Journal of Personalized Medicine·Lindsay M HendersonKenneth E Thummel
Nov 3, 1998·Clinical Pharmacology and Therapeutics·M P NowakR F Tyndale
Nov 8, 2001·Canadian Journal of Physiology and Pharmacology·A GaedigkJ S Leeder
Oct 23, 2013·Drug Metabolism and Drug Interactions·Martha Sosa-Macías, Adrián Llerena

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