title: High frequency of occurrence of CYP2D6 gene duplication/multiduplication indicating ultrarapid metabolism among suicide cases.
abstract: In Sweden, about 550 individuals die every year of drug intoxication. Many of these drugs are metabolized by CYP enzymes such as CYP2D6 and CYP2C19. A lack of these enzymes, resulting in poor metabolism, can lead to adverse reactions and even to fatality. On the other hand, an ultrarapid metabolism can lead to insufficient drug plasma concentration, resulting in failure of treatment, or it can lead to high concentrations of active/toxic metabolites. The aim of this project was to study the genetic profile of individuals with regard to the presence of CYP2D6 and CYP2C19 genes, in cases of fatal intoxication (242), suicide (intoxications excluded) (262), and natural death (212). PCR, followed by pyrosequencing, was used for all the analyses. We found that, among those who died of suicide (suicide cases), there was a higher number carrying more than two active CYP2D6 genes (corresponding to the phenotype of ultrarapid metabolizer) as compared with those who died of natural causes (natural-death cases) (P = 0.007).
authors.affiliation: Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden. anna-lena.zackrisson@rmv.se
authors.forename: A L
authors.initials: AL
authors.lastname: Zackrisson
authors.forename: B
authors.initials: B
authors.lastname: Lindblom
authors.forename: J
authors.initials: J
authors.lastname: Ahlner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D002423:Cause of Death; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D020440:Gene Duplication; D006801:Humans; D008297:Male; D008875:Middle Aged; D004364:Pharmaceutical Preparations / Q000378:metabolism; D016133:Polymerase Chain Reaction / Q000379:methods; D017422:Sequence Analysis, DNA / Q000379:methods; D013405:Suicide; D013548:Sweden / Q000453:epidemiology; D055815:Young Adult
chemical_list: D004364:Pharmaceutical Preparations; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6