Understanding Pharmacogenetic Variability

forensic toxicology working group members July 22, 2016 Forensic Toxicology

Article overview: This article explains Understanding Pharmacogenetic Variability and the scientific, legal or practical evidence readers should understand.

How genetics can change drug metabolism and response

Okorie Okorocha Discusses Pharmacogenetic Variability Pharmacogenetics is the study of how genes affect a person’s response to drugs. It is a relatively new field combining pharmacology and genomics. Pharmacology is a branch of medicine that examines the uses, effects, and modes of action of drugs while genomics concerns the sequencing and analysis of an organism’s genome. Genes are basically instructions, written in DNA, for building protein molecules. Different people can have different versions or slightly different DNA sequences, of the same gene. Some of these variations are common while others are rare. Pharmacogenomics looks at these gene variations and how they impact on drug responses. Drug-Specific Evidence, Not a Universal Genetic Percentage Genetic effects must be assessed for the specific drug and outcome. The FDA separates associations relevant to drug response or adverse reactions from associations supported only by pharmacokinetic data. A change in drug concentration does not, by itself, establish a clinical effect. Codeine: Poor and Ultrarapid Metabolism Are Different The FDA Table of Pharmacogenetic Associations distinguishes two CYP2D6 patterns for codeine:

Poor metabolizers: Lower concentrations of the active metabolite may reduce effectiveness.
Ultrarapid metabolizers: Higher concentrations of the active metabolite increase the risk of adverse reactions, including life-threatening respiratory depression and death.

The earlier example suggesting that unusually fast codeine metabolism simply explains inadequate pain relief was misleading. It has been replaced rather than used to draw conclusions about an individual patient. Genotype is one factor in treatment decisions, not a guarantee that a medication will be safe or effective. Inclusion in the FDA table does not automatically mean testing is recommended before prescribing. Patients should not change medication without their prescriber. Editorial correction, October 3, 2026: This section was revised with AI assistance using the FDA source linked above. Personal review of this revision by Okorie Okorocha has not been established. This is educational information, not individual treatment advice. Pharmacogenetics may seem rather technical and it is necessary to have an expert explain the details in court. If you think the above information may be useful to your case, Okorie Okorocha can help you! For further information, see Chapter 7: Pharmacogenetics by Mary V. Relling; Kathleen M. Giacomini. Also see Pharmacogenetics Fact Sheet by the National Institute of General Medical Sciences at https://www.nigms.nih.gov/education/Pages/factsheet-pharmacogenomics.aspx.

Authoritative pharmacogenetics resources

FDA Table of Pharmacogenetic Associations — gene–drug associations evaluated by the FDA for effects on metabolism, response or adverse-event risk.
FDA Pharmacogenomic Biomarkers in Drug Labeling — pharmacogenomic information appearing in approved drug labeling.
NCBI Medical Genetics Summaries: Introduction — an evidence-based, regularly updated overview of genetic variants and drug response.
Clinical Pharmacogenetics Implementation Consortium guidelines — peer-reviewed gene–drug guidance for translating genetic results into prescribing decisions.

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