Suicide is a very serious act and risk factors have been classified as psychiatric, environmental or biological. It has been suggested that CYP2D6 gene involvement in the impact on suicidality may be due to unsuccessfully outcome of antidepressant therapy in ultrarapid metabolizers. An alternative explanation is based on CYP2D6 role in the metabolism of endogenous brain substrates which could affect psychological functioning (personality, cognitive functions and vulnerability to psycopathology). Actually, previous studies showed a high frequency of CYP2D6 duplication/multiduplication among suicide cases and attempters. The present preliminary study investigates CYP2D6 polymorphism in autopsy samples from suicide cases evaluating the enzymatic activity based on the number of active alleles. Blood or buccal swabs from suicide cases (33 out of 57) were analyzed. Whole CYP2D6 gene has been amplified by long-PCR, and 11 relevant single nucleotide polymorphisms (SNPs) were detected by minisequencing in order to identify the most common alleles showing different enzymatic activity. Samples were separated on an ABI 310 Genetic Analyzer and quantitative information derived from electropherograms was employed to establish the phase of gene duplication in heterozygous individuals. Phenotypes were predicted according to the number of active alleles and individuals were grouped in four enzymatic activity classes. Results were compared with published data using Fisher's Exact test performed by RXC software. p-Values double left arrow 0.05 were regarded as significant. Our preliminary results are in agreement with previously published data showing a higher proportion of individuals carrying more than two active CYP2D6 genes among suicide death cases compared with natural death cases. Despite the limited number of tested individuals in our preliminary study, also due to the DNA quality in forensic samples, the higher number of ultrarapid metabolizers in suicide cases seems to confirm an association between CYP2D6 genetic polymorphism and suicide. Further studies increasing the suicidal sample are needed to verify the data and to look for an explanation.
Riccardi L.N., Lanzellotto R., Ceccardi S., Bini C., Fersini F., Govi A., et al. (2013). CYP2D6 Polymorphism in Suicide Cases. Bologna : Monduzzi Editore.
CYP2D6 Polymorphism in Suicide Cases
RICCARDI, LAURA NATALIA;CECCARDI, STEFANIA;BINI, CARLA;GOVI, ANNAMARIA;INGRAVALLO, FRANCESCA;PELOTTI, SUSI
2013
Abstract
Suicide is a very serious act and risk factors have been classified as psychiatric, environmental or biological. It has been suggested that CYP2D6 gene involvement in the impact on suicidality may be due to unsuccessfully outcome of antidepressant therapy in ultrarapid metabolizers. An alternative explanation is based on CYP2D6 role in the metabolism of endogenous brain substrates which could affect psychological functioning (personality, cognitive functions and vulnerability to psycopathology). Actually, previous studies showed a high frequency of CYP2D6 duplication/multiduplication among suicide cases and attempters. The present preliminary study investigates CYP2D6 polymorphism in autopsy samples from suicide cases evaluating the enzymatic activity based on the number of active alleles. Blood or buccal swabs from suicide cases (33 out of 57) were analyzed. Whole CYP2D6 gene has been amplified by long-PCR, and 11 relevant single nucleotide polymorphisms (SNPs) were detected by minisequencing in order to identify the most common alleles showing different enzymatic activity. Samples were separated on an ABI 310 Genetic Analyzer and quantitative information derived from electropherograms was employed to establish the phase of gene duplication in heterozygous individuals. Phenotypes were predicted according to the number of active alleles and individuals were grouped in four enzymatic activity classes. Results were compared with published data using Fisher's Exact test performed by RXC software. p-Values double left arrow 0.05 were regarded as significant. Our preliminary results are in agreement with previously published data showing a higher proportion of individuals carrying more than two active CYP2D6 genes among suicide death cases compared with natural death cases. Despite the limited number of tested individuals in our preliminary study, also due to the DNA quality in forensic samples, the higher number of ultrarapid metabolizers in suicide cases seems to confirm an association between CYP2D6 genetic polymorphism and suicide. Further studies increasing the suicidal sample are needed to verify the data and to look for an explanation.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
