Related Experiment Video
Updated: May 25, 2026
07:15
Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
Published on: January 16, 2019
Testing for variants in CYP2C19: population frequencies and testing experience in a clinical laboratory
Charles M Strom1, Dana Goos, Beryl Crossley
1Genetic Testing Center, Nichols Institute Quest Diagnostics, San Juan Capistrano, California, USA. Charles.M.Strom@QuestDiagnostics.com
Summary
Cytochrome P450 2C19 (CYP2C19) genotype frequencies vary significantly across US ethnic groups. A notable percentage of individuals possess clinically actionable genotypes, impacting drug metabolism.
Area of Science:
- Pharmacogenomics
- Clinical Chemistry
- Population Genetics
Background:
- Cytochrome P450 2C19 (CYP2C19) is a key enzyme in drug metabolism.
- Genetic variations in CYP2C19 influence drug efficacy and safety.
- Understanding ethnic-specific genotype frequencies is crucial for personalized medicine.
Purpose of the Study:
- To determine CYP2C19 variant allele genotype frequencies in diverse US populations.
- To identify the prevalence of clinically actionable CYP2C19 genotypes.
- To analyze ethnic variations in allele frequencies.
Main Methods:
- Analysis of 1,396 anonymized samples from CYP2C19 genotyping tests.
- Inclusion of samples from White, African American, Hispanic, and Ashkenazi Jewish individuals.
- Genotype and phenotype prediction from stored analytical results.
Main Results:
- Significant ethnic differences observed in the CYP2C19 *17 ultrarapid allele frequencies.
- Pan-ethnic population: 3.8% ultrarapid, 24% extensive, 27% intermediate, 3.5% poor metabolizers.
- 7.3% of individuals had clinically actionable genotypes; *17 allele found on various backgrounds (*1, *2, *4).
Conclusions:
- CYP2C19 genotype frequencies exhibit considerable ethnic variability within the US.
- A substantial proportion of the population may have actionable genotypes impacting drug response.
- These findings support the need for ethnic-specific pharmacogenomic data in clinical practice.
Related Concept Videos
01:28Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes
Cytochrome P450 (CYP450) enzymes are a superfamily of heme-containing monooxygenases that play a pivotal role in Phase I drug metabolism by catalyzing oxidation and reduction reactions.These enzymes transform lipophilic xenobiotics into more hydrophilic metabolites, facilitating subsequent Phase II conjugation and eventual excretion. The CYP450 family is classified into families (e.g., CYP1–CYP3) and subfamilies (e.g., CYP2A, CYP2C), based on amino acid sequence homology.CYP450 isoenzymes,...
01:27Pharmacogenetics of Drug Metabolism: Overview
Genetic polymorphism in drug metabolism is crucial to the inter-individual variability observed in drug responses. Drug metabolism primarily involves the chemical modification of drugs and other xenobiotics to enhance their elimination by increasing their polarity. Two main classes of enzymes mediate this biotransformation process: Phase I enzymes, primarily cytochrome P450s, catalyze oxidation and reduction reactions, while other enzymes, such as esterases, mediate hydrolysis, and Phase II...
01:27Principles of Pharmacogenetics: Types of Genetic Variants
The human genome is over 99.9% identical between individuals, yet genetic differences exist at millions of bases. The human genome contains approximately 3 million variant positions per individual, many of which are heterozygous, contributing to genetic diversity and individual traits. Genetic variations include single-nucleotide polymorphisms (SNPs), insertions, deletions, and copy number variations (CNVs).SNPs, the most common variation, involve single-base changes in DNA. These can be...
01:29Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
01:29Pharmacogenomics: Identification of New Drug Targets
Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...
02:26Comparing Copy Number Variations and SNPs
Sequencing of the human genome has opened up several best-kept secrets of the genome. Scientists have identified thousands of genome variations that exist within a population. These variations can be a single nucleotide or a larger chromosomal variation.
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...