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Physiogenomic analysis of CYP450 drug metabolism correlates dyslipidemia with pharmacogenetic functional status in psychiatric patients.
- Source :
-
Biomarkers in medicine [Biomark Med] 2011 Aug; Vol. 5 (4), pp. 439-49. - Publication Year :
- 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.<br />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.<br />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.<br />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.
- Subjects :
- Adolescent
Adult
Aged
Aryl Hydrocarbon Hydroxylases genetics
Aryl Hydrocarbon Hydroxylases metabolism
Biomarkers blood
Body Mass Index
Cholesterol, HDL blood
Cholesterol, LDL blood
Cohort Studies
Cytochrome P-450 CYP2C19
Cytochrome P-450 CYP2C9
Cytochrome P-450 CYP2D6 genetics
Cytochrome P-450 CYP2D6 metabolism
Cytochrome P-450 Enzyme System genetics
Depressive Disorder, Major complications
Depressive Disorder, Major drug therapy
Depressive Disorder, Major metabolism
Dyslipidemias complications
Female
Genotype
Humans
Male
Middle Aged
Polymorphism, Single Nucleotide
Psychotropic Drugs therapeutic use
Risk Factors
Triglycerides blood
Cytochrome P-450 Enzyme System metabolism
Dyslipidemias metabolism
Psychotropic Drugs metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1752-0371
- Volume :
- 5
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Biomarkers in medicine
- Publication Type :
- Academic Journal
- Accession number :
- 21861666
- Full Text :
- https://doi.org/10.2217/bmm.11.33