Molecular genetic identification of the major CYP2D6 alleles and utilization in psychiatric treatment of depression



Year of publication 2009
Type Article in Periodical
Magazine / Source European Journal of Human Genetics
MU Faculty or unit

Faculty of Medicine

Description The gene CYP2D6 encodes enzyme involved in biotransformation of psychotropics in psychiatric treatment. The Caucasian population has been grouped in according to the enzymatic activity as poor, intermediate, effective and ultrarapid metabolizers. The determination of metabolic activity prior the dose adjustment could be really useful in some cases. The methodical approach of genotyping is based on long PCR and subsequent sequencing. These standard methods are combinated with RealTimePCR and High Resolution Melting analysis (HRM) using Light Cycler 480 System. Recently is possible to detect the most frequent null alleles 3* 4* 6* 7* and 8*. Allele 5* could be detected by using agarose electrophoresis or UPL probes. HRM analysis has been performed for the most frequent SNPs in CYP2D6 gene as a fast cheap and reliable method for pre-genotyping. O-demethylation of dextromethorfan was used for metabolic activity assesment. The concentrations of marker and metabolite in the urine were determined by HPLC assay. The phenotypes PM and EM were distinguished by using 0,3 antimode. The clinical data were analyzed and compared with genotype and phenotype result. This paper provides an overview of current technologies available for CYP2D6 genotype and phenotype testing and the result of testing of the group of 91 patients, treated with Paroxetine. The effect of Paroxetine treatment on CYP2D6 is summarized in Table 1. Supported by research project MSM 0021622404 (2005 - 2011)

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