Physiogenomic analysis of CYP450 drug metabolism correlates dyslipidemia with pharmacogenetic functional status in psychiatric patients.
Publication/Presentation Date
8-1-2011
Abstract
AIMS: To investigate associations between novel human cytochrome P450 (CYP450) combinatory (multigene) and substrate-specific drug metabolism indices, and elements of metabolic syndrome, such as low density lipoprotein cholesterol (LDLc), high density lipoprotein cholesterol (HDLc), triglycerides and BMI, using physiogenomic analysis.
METHODS: CYP2C9, CYP2C19 and CYP2D6 genotypes and clinical data were obtained for 150 consecutive, consenting hospital admissions with a diagnosis of major depressive disorder and who were treated with psychotropic medications. Data analysis compared clinical measures of LDLc, HDLc, triglyceride and BMI with novel combinatory and substrate-specific CYP450 drug metabolism indices.
RESULTS: We found that a greater metabolic reserve index score is related to lower LDLc and higher HDLc, and that a greater metabolic alteration index score corresponds with higher LDLc and lower HLDc values. We also discovered that the sertraline drug-specific indices correlated with cholesterol and triglyceride values.
CONCLUSIONS: Overall, we demonstrated how a multigene approach to CYP450 genotype analysis yields more accurate and significant results than single-gene analyses. Ranking the individual with respect to the population represents a potential tool for assessing risk of dyslipidemia in major depressive disorder patients who are being treated with psychotropics. In addition, the drug-specific indices appear useful for modeling a variable of potential relevance to an individual's risk of drug-related dyslipidemia.
Volume
5
Issue
4
First Page
439
Last Page
449
ISSN
1752-0371
Published In/Presented At
Ruaño, G., Villagra, D., Szarek, B., Windemuth, A., Kocherla, M., Gorowski, K., Berrezueta, C., Schwartz, H. I., & Goethe, J. (2011). Physiogenomic analysis of CYP450 drug metabolism correlates dyslipidemia with pharmacogenetic functional status in psychiatric patients. Biomarkers in medicine, 5(4), 439–449. https://doi.org/10.2217/bmm.11.33
Disciplines
Medicine and Health Sciences
PubMedID
21861666
Department(s)
Fellows and Residents
Document Type
Article
