Frequency of "Poor Transporter" Phenotype Among Patients with Mental Disorders: Pilot Study

Abstract

The problem of psychopharmacotherapy safety is actively studied, but remains unresolved, despite the development of new generations of psychotropic drugs (PDs). Neurotoxic adverse drug reactions (ADRs) are one of the leading causes of pseudo-resistance of mental disorders and patient disability. The development of neurotoxic ADRs is genetically determined, and caused by a slowdown in the efflux of PDs from the brain into the blood through the blood-brain barrier. Of the three transport proteins involved in the efflux of PDs, the most clinically significant and studied is glycoprotein P, encoded by the MDR1 (ABCB1) gene. This transport protein is involved in the efflux of a large number of PDs used in real clinical practice of a psychiatrist. Objective: To study the frequency of the non-functional allele 3435T of the single-nucleotide variant rs1045642 of the MDR1 (ABCB1) gene in patients with mental disorders living in the Northwestern region of the Russia. Methods: The study included 71 Caucasians patients with mental disorders (34 male and37 female). Mean age of the study participants was 35.1±16 years). Real-time polymerase chain reaction used for pharmacogenetic testing. Results: The frequency of the nonfunctional homozygous genotype 3435TT (phenotype "poor transporter") was 19.7%, and the frequency of the low-functional heterozygous genotype 3435CT (phenotype "intermediate transporter") was 57.7%. The allelic frequency of T rs1045642 of the MDR1 (ABCB1) gene in Caucasians patients with mental disorders living in the Northwestern region of the Russia was 97.1%. Conclusions: The frequency the nonfunctional allele 3435T of the MDR1 (ABCB1) gene associated with a slowdown in PDs efflux through BBB in patients with mental disorders living in the Northwestern region of the Russia is high, which explains the need for a wider introduction of this method of personalized medicine into real psychiatric practice.