NDLI: Novel drug metabolism indices for pharmacogenetic functional status based on combinatory genotyping of CYP2C9, CYP2C19 and CYP2D6 genes.

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Novel drug metabolism indices for pharmacogenetic functional status based on combinatory genotyping of CYP2C9, CYP2C19 and CYP2D6 genes.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Villagra, David Goethe, John Schwartz, Harold I. Szarek, Bonnie Kocherla, Mohan Gorowski, Krystyna Windemuth, Andreas Ruaño, Gualberto
Description	Country affiliation: United States Author Affiliation: Villagra D ( Genomas Inc., Hartford, CT, USA.)
Abstract	AIMS: We aim to demonstrate clinical relevance and utility of four novel drug-metabolism indices derived from a combinatory (multigene) approach to CYP2C9, CYP2C19 and CYP2D6 allele scoring. Each index considers all three genes as complementary components of a liver enzyme drug metabolism system and uniquely benchmarks innate hepatic drug metabolism reserve or alteration through CYP450 combinatory genotype scores. METHODS: A total of 1199 psychiatric referrals were genotyped for polymorphisms in the CYP2C9, CYP2C19 and CYP2D6 gene loci and were scored on each of the four indices. The data were used to create distributions and rankings of innate drug metabolism capacity to which individuals can be compared. Drug-specific indices are a combination of the drug metabolism indices with substrate-specific coefficients. RESULTS: The combinatory drug metabolism indices proved useful in positioning individuals relative to a population with regard to innate drug metabolism capacity prior to pharmacotherapy. Drug-specific indices generate pharmacogenetic guidance of immediate clinical relevance, and can be further modified to incorporate covariates in particular clinical cases. CONCLUSIONS: We believe that this combinatory approach represents an improvement over the current gene-by-gene reporting by providing greater scope while still allowing for the resolution of a single-gene index when needed. This method will result in novel clinical and research applications, facilitating the translation from pharmacogenomics to personalized medicine, particularly in psychiatry where many drugs are metabolized or activated by multiple CYP450 isoenzymes.
File Format	HTM / HTML
ISSN	17520363
e-ISSN	17520371
DOI	10.2217/bmm.11.32
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 Aryl Hydrocarbon Hydroxylases Genetics Cytochrome P-450 Cyp2d6 Pharmaceutical Preparations Metabolism Adolescent Alleles Child, Preschool Cytochrome P-450 Cyp2c19 Cytochrome P-450 Cyp2c9 Genetic Association Studies Genetic Loci Genotype Polymorphism, Single Nucleotide 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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