Prediction of codeine toxicity in infants and their mothers using a novel combination of maternal genetic markers

Sistonen, J; Madadi, P; Ross, C J; Yazdanpanah, M; Lee, J W; Landsmeer, M L A; Nauta, M; Carleton, B C; Koren, G; Hayden, M R (2012). Prediction of codeine toxicity in infants and their mothers using a novel combination of maternal genetic markers. Clinical pharmacology & therapeutics, 91(4), pp. 692-9. New York, N.Y.: Nature Publishing Group 10.1038/clpt.2011.280

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute of Clinical Chemistry

UniBE Contributor:

Sistonen, Johanna

ISSN:

0009-9236

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:36

Last Modified:

17 Mar 2015 21:27

Publisher DOI:

10.1038/clpt.2011.280

PubMed ID:

22398969

Web of Science ID:

000301891800021

URI:

https://boris.unibe.ch/id/eprint/14667 (FactScience: 221752)

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