NDLI: Physiogenomic analysis of CYP450 drug metabolism correlates dyslipidemia with pharmacogenetic functional status in psychiatric patients.

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Physiogenomic analysis of CYP450 drug metabolism correlates dyslipidemia with pharmacogenetic functional status in psychiatric patients.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Ruaño, Gualberto Villagra, David Szarek, Bonnie Windemuth, Andreas Kocherla, Mohan Gorowski, Krystyna Berrezueta, Christopher Schwartz, Harold I. Goethe, John
Description	Country affiliation: United States Author Affiliation: Ruaño G ( Genomas Inc., Hartford, CT 06106, USA. gruano@harthosp.org)
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.
File Format	HTM / HTML
ISSN	17520363
e-ISSN	17520371
DOI	10.2217/bmm.11.33
Journal	Biomarkers in Medicine
Issue Number	4
Volume Number	5
Language	English
Publisher	Future Science Group
Publisher Date	2011-08-01
Publisher Place	Great Britain (UK)
Access Restriction	Open
Subject Keyword	Discipline Biochemistry Cytochrome P-450 Enzyme System Metabolism Dyslipidemias Psychotropic Drugs Adolescent Aryl Hydrocarbon Hydroxylases Genetics Biological Markers Blood Body Mass Index Cholesterol, Hdl Cholesterol, Ldl Cohort Studies Cytochrome P-450 Cyp2c19 Cytochrome P-450 Cyp2c9 Cytochrome P-450 Cyp2d6 Depressive Disorder, Major Complications Drug Therapy Genotype Polymorphism, Single Nucleotide Therapeutic Use Risk Factors Triglycerides Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Biochemistry (medical) Drug Discovery Clinical Biochemistry

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