Analysis of CYP2D6 gene variation in Venezuelan population: Implications for forensic toxicology

Slow drug degradation by CYP enzymes can lead to its accumulation in the body with subsequent toxic effects. CYP2D6 is involved in the metabolism of many toxicologically important drugs such as tricyclic antidepressants, commonly implicated in fatal drug poisonings. Since in human populations the gene coding for this enzyme exhibits high genetic polymorphism, they are of major pharmacogenetic importance. The aim of this work is to describe the distribution of genetic polymorphisms of CYP2D6 responsible for poor and intermediate metabolizers phenotypes in Venezuelan population and provide guidance on the importance of conducting postmortem forensic examinations to elucidate the role of genetic variation in drug intoxications. We carried out the analysis of CYP2D6*3, *4, *5, *6 and 10* alleles of 110 unrelated healthy individuals by allele-specific PCR tetra-primer. The allelic frequencies obtained for *4 (15.9%) and *10 (16.4%) in the Venezuelan population highlights the importance of CYP2D6 genotyping in cases where a high concentration of a drug metabolized by this route has been used, without suspicion of acute overdose.