[CYP2D6 gene polymorphism in psychiatric patients resistant to standard pharmacotherapy].
The debrisoquine polymorphism is a genetic variation in oxidative drug metabolism mediated by CYP2D6 gene, characterized by two phenotypes, the extensive metabolizer (EM) and poor metabolizer (PM). PM phenotype is inherited as autosomal recessive trait and occurs in 5-10% of Caucasian population. It is associated with the inefficient metabolism of over 30 drugs, including many psychotropic drugs. Clinical studies shown that PM are at higher risk than EM of adverse reactions to these drugs. We genotyped 22 psychiatric patients in whom standard pharmacotherapy had failed or drug adverse events occurred and in 14 patients in whom standard therapy was successful. CYP2D6 polymorphic alleles were identified using allele specific nested PCR reaction. The PM genotype was found in 4 of 22 (18%) patients resistant to standard pharmacotherapy and in none of 14 patients with improvement after standard therapy. Unsuccessful standard psychotropic drugs therapy in psychiatric patients may be associated with PM phenotype.
Zabrocka
M
M
I Kliniki Psychiatrycznej AM w Lodzi.
Woszczek
G
G
Borowiec
M
M
Rabe-Jabłońska
J
J
Kowalski
M L
ML
D000328:Adult; D000368:Aged; D000483:Alleles; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D004252:DNA Mutational Analysis; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005260:Female; D015870:Gene Expression / Q000235:genetics; D005787:Gene Frequency; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000188:drug therapy* / Q000235:genetics*; D008875:Middle Aged; D017354:Point Mutation / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D011619:Psychotropic Drugs / Q000627:therapeutic use*
D011619:Psychotropic Drugs; D019389:Cytochrome P-450 CYP2D6