Document Detail


CYP2D6-related oxidation polymorphism in a Canadian Inuit population.
MedLine Citation:
PMID:  9164697     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 of the CYP2D6 polymorphism in Canadian Inuit, while the frequencies of allelic variants of CYP2D6 point to the uniqueness of this population. Several important therapeutic drugs that are being prescribed in Arctic communities will have altered pharmacokinetics in PMs of CYP2D6.
Authors:
M Jurima-Romet; B C Foster; W L Casley; A Rode; P Vloshinsky; H S Huang; S Geertsen
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Canadian journal of physiology and pharmacology     Volume:  75     ISSN:  0008-4212     ISO Abbreviation:  Can. J. Physiol. Pharmacol.     Publication Date:  1997 Mar 
Date Detail:
Created Date:  1997-07-15     Completed Date:  1997-07-15     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  0372712     Medline TA:  Can J Physiol Pharmacol     Country:  CANADA    
Other Details:
Languages:  eng     Pagination:  165-72     Citation Subset:  IM    
Affiliation:
Bureau of Drug Research, Drugs Directorate, Health Canada, Ottawa, ON, Canada.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Aged
Alleles
Canada
Cytochrome P-450 CYP2D6 / genetics*,  metabolism
Dextromethorphan / metabolism,  urine
Female
Genotype
Humans
Inuits / genetics*
Male
Middle Aged
Phenotype
Polymorphism, Genetic*
Chemical
Reg. No./Substance:
125-71-3/Dextromethorphan; EC 1.14.14.1/Cytochrome P-450 CYP2D6

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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