Pharmacogenetics of Cytochrome P450 Enzymes in American Indian and Caucasian Children Admitted to a Psychiatric Hospital

Objective: The cytochrome P450 (CYP450) enzyme system metabolizes many psychiatric medications. We compare frequencies of alleles and phenotypes for CYP2D6, CYP2C9, and CYP2C19 in American Indian (AI) and Caucasian youth treated at a psychiatric hospital in the Northwestern United States. Methods: A retrospective chart review evaluated CYP450 pharmacogenetic (PGx) data from the Shodair Children's Hospital Clinical Genetic Laboratory between 2006 and 2014. CYP2D6 genotyping was performed using the xTAG® CYP2D6 Kit (Luminex, Austin, TX). CYP2C9 and CYP2C19 genotyping was performed by laboratory-developed assays using allele-specific quantitative polymerase chain reaction (qPCR) and/or melt-curve analysis. Results: A total of 123 AIs and 688 Caucasians met criteria for inclusion. The overall prevalence of CYP2D6 poor metabolizers was 8.3% (95% Confidence Interval [CI] 6.1%, 10.4%), 9.3% in Caucasians (95% CI 7.1%, 11.5%), and 2.4% in AIs (95% CI 0%, 5.2%). The overall prevalence of CYP2D6 ultrarapid metabolizers was 1.6% (95% CI 0.7%, 2.5%), 1.6% in the Caucasians (95% CI 0.7%, 2.5%), and 1.6% in AIs (95% CI 0%, 3.9%). The overall prevalence of CYP2C9 poor metabolizers was 3% (95% CI 1.7%, 4.2%), 3.2% in Caucasians (95% CI 1.8%, 4.6%), and 1.8% in AIs (95% CI 0%, 4.2%). The overall prevalence of CYP2C19 poor metabolizers was 2.5% (95% CI 1.3%, 3.6%), 2.9% in Caucasians (95% CI 1.6%, 4.2%), and 0% in AIs. The overall prevalence of CYP2C19 ultrarapid metabolizers was 1.5% (95% CI 0.6%, 2.4%), 1.6% in Caucasians (95% CI 0.6%, 2.6%), and 0.9% in AIs (95% CI 0%, 2.6%). Conclusions: This study is the first to identify differences in polymorphism frequencies of the CYP450 system in AIs and Caucasian youth admitted to a psychiatric hospital. Our findings warrant further study of these populations to determine if these differences are generalizable to the larger population of Caucasian and AI/Alaska Native youth in the Northwestern United States.