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.
AIMS: To investigate associations between novel humancytochrome 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 disorderpatients 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.
Authors: G Ruaño; J W Goethe; C Caley; S Woolley; T R Holford; M Kocherla; A Windemuth; J de Leon Journal: Mol Psychiatry Date: 2007-01-02 Impact factor: 15.992
Authors: Jenny E Kootstra-Ros; Marga J M Van Weelden; John W J Hinrichs; Peter A G M De Smet; Jan van der Weide Journal: J Clin Pharmacol Date: 2006-11 Impact factor: 3.126
Authors: David Villagra; John Goethe; Harold I Schwartz; Bonnie Szarek; Mohan Kocherla; Krystyna Gorowski; Andreas Windemuth; Gualberto Ruaño Journal: Biomark Med Date: 2011-08 Impact factor: 2.851
Authors: Gualberto Ruaño; Bonnie L Szarek; David Villagra; Krystyna Gorowski; Mohan Kocherla; Richard L Seip; John W Goethe; Harold I Schwartz Journal: Biomark Med Date: 2013-06 Impact factor: 2.851