Document Detail


Prediction of Codeine Toxicity in Infants and Their Mothers Using a Novel Combination of Maternal Genetic Markers.
MedLine Citation:
PMID:  22398969     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Substantial variation exists in response to standard doses of codeine ranging from poor analgesia to life-threatening central nervous system (CNS) depression. We aimed to discover the genetic markers predictive of codeine toxicity by evaluating the associations between polymorphisms in cytochrome P450 2D6 (CYP2D6), UDP-glucuronosyltransferase 2B7 (UGT2B7), P-glycoprotein (ABCB1), mu-opioid receptor (OPRM1), and catechol O-methyltransferase (COMT) genes, which are involved in the codeine pathway, and the symptoms of CNS depression in 111 breastfeeding mothers using codeine and their infants. A genetic model combining the maternal risk genotypes in CYP2D6 and ABCB1 was significantly associated with the adverse outcomes in infants (odds ratio (OR) 2.68; 95% confidence interval (CI) 1.61-4.48; P(trend) = 0.0002) and their mothers (OR 2.74; 95% CI 1.55-4.84; P(trend) = 0.0005). A novel combination of the genetic and clinical factors predicted 87% of the infant and maternal CNS depression cases with a sensitivity of 80% and a specificity of 87%. Genetic markers can be used to improve the outcome of codeine therapy and are also probably important for other opioids sharing common biotransformation pathways.
Authors:
J Sistonen; P Madadi; C J Ross; M Yazdanpanah; J W Lee; M L A Landsmeer; M Nauta; B C Carleton; G Koren; M R Hayden
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-3-07
Journal Detail:
Title:  Clinical pharmacology and therapeutics     Volume:  -     ISSN:  1532-6535     ISO Abbreviation:  -     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-3-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372741     Medline TA:  Clin Pharmacol Ther     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1] Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada [2] Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada [3] Institute of Clinical Chemistry, Inselspital, Bern University Hospital, and University of Bern, Bern, Switzerland.
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