Pharmacogenomics
Definition
Study of how inherited variation in drug-metabolising genes (CYP2D6, CYP2C19, NAT2, G6PD) changes drug response. The Indian Genome Variation Consortium and ICMR have mapped several of these variants in Indian populations.
- Key genes
- CYP2D6, CYP2C19, NAT2, G6PD
- Effect studied
- Inherited variation in drug metabolism and response
- India data source
- Indian Genome Variation Consortium, ICMR
- Forensic relevance
- Explains individual variability in poisoning severity
Common questions
How does pharmacogenomics affect interpretation of a poisoning case?+
A person's genotype for drug-metabolising enzymes can make an otherwise typical dose unexpectedly toxic or, conversely, allow survival of a dose that would be fatal to most people, which toxicologists factor in when explaining a discrepancy between dose and outcome.
Can relevant metabolising-enzyme genotypes be tested from post-mortem samples?+
Yes, genetic testing for common variants in these enzymes can be performed on post-mortem blood or tissue, though it is not part of routine toxicology and is usually requested only when metabolism-related variability needs to be explained.
Related terms
- First-Pass Metabolism
- Hepatic and gut wall biotransformation of orally absorbed drug before it reaches systemic circulation. Bypassed by IV, intramuscular, inhalation and most dermal...
- Idiosyncrasy
- A qualitatively abnormal response to a normal dose, traceable to genetic polymorphism in metabolising enzymes, transporters or receptor targets. Not the same...
- LD50
- Median lethal dose; the dose of a substance that kills 50% of a test population, expressed as mg/kg body weight. The classical...
- Tolerance
- Reduced response to a given dose after repeated exposure. Pharmacokinetic tolerance is enzyme induction or transporter upregulation; pharmacodynamic tolerance is receptor downregulation...
- Volume of Distribution (Vd)
- The apparent volume in which a drug is distributed in the body, calculated as dose divided by plasma concentration at time zero....