Genetic polymorphism of cytochrome 450 (CYP) drug-metabolizing enzymes leads to inter-individual variability in the plasma concentrations of many drugs. Inter-individual variability among patients is a major clinical problem, as it can cause serious adverse drug reactions or therapeutic failures.
Everyone is different, because of the genome diversity. This fact influences the efficiency of medicine and therefore genotyping should help in the field of potential therapeutics testing or in personalized medicine.
Genotyping is the process of determining differences in the genetic make-up (genotype) of an individual by examining the individual’s DNA sequence and comparing it to another individual’s sequence or a reference sequence.
Genotyping applies to a broad range of individuals, including microorganisms. For example, viruses and bacteria can be genotyped. Genotyping in this context may help in controlling the spreading of pathogens, by tracing the origin of outbreaks.
Example 1: Cytochrome P450 genytyping
An important test for new drug candidates is xenobiotic biotransformation. In this field cytochrome P450 (CYP) enzymes play crucial role. Individual CYP activity may also be affected by different xenobiotics – either induction or inhibition of distinct CYP isoenzyme may cause failure or toxicity of pharmacotherapy. Therefore activity testing prior to genotyping is tested.
CYP2A6 contain more than 20 basic variants, most important are alleles 1, 2, 4, 9 and 12. Which are connected in drug metabolism. And for each allele different analytical method is used (real-time PCR with dual labelled probe or real-time PCR using SYBR green followed by melting analysis).
For better understanding and appropriate interpretation biochemical testing is complete with genotyping. For example genotyping of cytochrome CYP2A6 should be done. These data help in evaluation of biotransformation studies.
Topics on Drug Metabolism (2012), InTech, ISBN 978-953-51-0099-7