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.,
Clinical Pharmacology and Therapeutics

Sistonen, J., Madadi, P., Ross, C. J., Yazdanpanah, M., Lee, J. W., Landsmeer, M., … Hayden, M. R. (2012). Prediction of codeine toxicity in infants and their mothers using a novel combination of maternal genetic markers. Clinical Pharmacology and Therapeutics, 91(4), 692–699. doi:10.1038/clpt.2011.280