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Cytochrome P450 variations in different ethnic populations
1Concordia University Wisconsin, School of Pharmacy, 12800 N. Lakeshore Drive, Mequon, WI 53022, USA. Joseph.mcgraw@cuw.edu
Expert Opinion on Drug Metabolism & Toxicology
|February 1, 2012
Summary
Genetic variations, known as single nucleotide polymorphisms (SNPs), significantly influence how individuals metabolize drugs via cytochrome P450 oxidase (CYP450) enzymes. Understanding SNP distribution across racial groups is key to predicting drug response variability.
Area of Science:
- Pharmacogenetics
- Drug Metabolism
- Genomics
Background:
- Drug response variability is a critical clinical challenge.
- Hepatic cytochrome P450 oxidase (CYP450) enzymes are major determinants of drug metabolism.
- Genetic variations, specifically single nucleotide polymorphisms (SNPs), explain much of this variability.
Purpose of the Study:
- To review the racial/ethnic distribution of key CYP450 SNPs (CYP1A2, 2C8/9/19, 2D6, 3A4/5).
- To examine the relationship between genotype and phenotype for these SNPs.
- To provide insight into how SNP prevalence impacts drug metabolism phenotypes across different populations.
Main Methods:
- Review of existing literature on CYP450 SNPs.
- Analysis of racial/ethnic distribution data for selected CYP450 SNPs.
- Correlation of SNP genotypes with observed metabolic phenotypes.
Main Results:
- Significant racial/ethnic differences exist in the distribution of CYP450 SNPs.
- These SNP distribution differences correlate with variations in metabolic phenotypes.
- Challenges in phenotypic characterization exist for CYP3A4/5 and 2C8/9 due to overlapping specificities and unidentified SNPs.
Conclusions:
- Racial/ethnic disparities in drug metabolic phenotypes are largely attributable to differing SNP distributions.
- Further research on newly identified, prevalent, and racially stratified SNPs is needed to fully elucidate CYP isoform-specific metabolism.
- Improved understanding will aid in personalized medicine approaches to drug therapy.
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