Worldwide Distribution of Cytochrome P450 Alleles: A Meta‐analysis of Population‐scale Sequencing Projects
Year: 2017
Type: review
Abstract: Genetic polymorphisms in cytochrome P450 (CYP) genes can result in altered metabolic activity toward a plethora of clinically important medications. Thus, single nucleotide variants and copy number variations in CYP genes are major determinants of drug pharmacokinetics and toxicity and constitute pharmacogenetic biomarkers for drug dosing, efficacy, and safety. Strikingly, the distribution of CYP alleles differs considerably between populations with important implications for personalized drug therapy and healthcare programs. To provide a global distribution map of CYP alleles with clinical importance, we integrated whole-genome and exome sequencing data from 56,945 unrelated individuals of five major human populations. By combining this dataset with population-specific linkage information, we derive the frequencies of 176 CYP haplotypes, providing an extensive resource for major genetic determinants of drug metabolism. Furthermore, we aggregated this dataset into spectra of predicted functional variability in the respective populations and discuss the implications for population-adjusted pharmacological treatment strategies.
DOI: 10.1002/cpt.690
Authors: Y Zhou, M Ingelman‐Sundberg, VM Lauschke
Institution: Karolinska Institutet
Language: English
Subfield: Pharmacology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,410
Funder: Vetenskapsrådet
Awards: Pharmacogenomic and epigenomic regulation of liver cell function, drug metabolism and drug response, Treatment of liver failure by generation of fully functional human hepatocytes via a proliferative intermediate, Functional human 3D in vitro models as new experimental paradigm for understanding drug-induced hepatotoxicity and liver disease
OpenAlex ID: W2605348885