Problems and prospects for the implementation of pharmacogenetic testing in real clinical practice in the Russian Federation

Насырова, Р. Ф.; Добродеева, В. С.; Skopin, S. D.; Shnayder, Nataliya; Neznanov, N.

doi:10.33920/med-01-2003-01

Cited by 10 publications

(4 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, the conclusion contains additional information that helps the psychiatrist decide whether to prescribe or cancel drugs in a particular patient. Thus, this PGx algorithm allows the psychiatrist to make a decision on the appointment of psychopharmacotherapy without the involvement of a clinical pharmacologist in most cases [77,78]. The disadvantages of this method are: the inability to study SNVs/polymorphisms of the genes encoding APs transport proteins; the absence of the cumulative effect of the studied SNVs/polymorphisms and assessment of several genes encoding APs transport proteins; the inability to fully characterize the genetically determined changes in the functional activity of this transport protein(s) and the level of its (their) expression in the BBB.…”

Section: Discussionmentioning

confidence: 99%

“…The results of DNA testing are provided to the patient and their attending physician within 8 working days, including recommendations for the selection and dosing of APs. This may help to increase the effectiveness and safety of psychopharmacotherapy [78].The disadvantages of this method are: the absence in the test of SNVs/polymorphisms of the genes encoding APs transport proteins; the impossibility of assessing the risk of decrease in the transport of APs through the membrane of neurons and the BBB; the impossibility of assessing genetically determined changes in the functional activity of the APs transport proteins and the level of their expression at the level of the BBB and endothelial cell membrane of target neurons of the action of APs.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Genetic Predictors of Antipsychotic Efflux Impairment via Blood-Brain Barrier: Role of Transport Proteins

Насырова

Shnayder

Osipova

et al. 2023

Genes

View full text Add to dashboard Cite

Antipsychotic (AP)—induced adverse drug reactions (ADRs) are a current problem of biological and clinical psychiatry. Despite the development of new generations of APs, the problem of AP-induced ADRs has not been solved and continues to be actively studied. One of the important mechanisms for the development of AP-induced ADRs is a genetically-determined impairment of AP efflux across the blood-brain barrier (BBB). We present a narrative review of publications in databases (PubMed, Springer, Scopus, Web of Science E-Library) and online resources: The Human Protein Atlas; GeneCards: The Human Gene Database; US National Library of Medicine; SNPedia; OMIM Online Mendelian Inheritance in Man; The PharmGKB. The role of 15 transport proteins involved in the efflux of drugs and other xenobiotics across cell membranes (P-gp, TAP1, TAP2, MDR3, BSEP, MRP1, MRP2, MRP3, MRP4, MRP5, MRP6, MRP7, MRP8, MRP9, BCRP) was analyzed. The important role of three transporter proteins (P-gp, BCRP, MRP1) in the efflux of APs through the BBB was shown, as well as the association of the functional activity and expression of these transport proteins with low-functional and non-functional single nucleotide variants (SNVs)/polymorphisms of the ABCB1, ABCG2, ABCC1 genes, encoding these transport proteins, respectively, in patients with schizophrenia spectrum disorders (SSDs). The authors propose a new pharmacogenetic panel “Transporter protein (PT)—Antipsychotic (AP) Pharmacogenetic test (PGx)” (PTAP-PGx), which allows the evaluation of the cumulative contribution of the studied genetic biomarkers of the impairment of AP efflux through the BBB. The authors also propose a riskometer for PTAP-PGx and a decision-making algorithm for psychiatrists. Conclusions: Understanding the role of the transportation of impaired APs across the BBB and the use of genetic biomarkers for its disruption may make it possible to reduce the frequency and severity of AP-induced ADRs, since this risk can be partially modified by the personalized selection of APs and their dosing rates, taking into account the genetic predisposition of the patient with SSD.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Genetic Predictors of Antipsychotic Efflux Impairment via Blood-Brain Barrier: Role of Transport Proteins

Насырова

Shnayder

Osipova

et al. 2023

Genes

View full text Add to dashboard Cite

show abstract

“…In different people, the set of the cytochrome P450 isoenzymes in the endoplasmic reticulum (ER) and on the inner mitochondrial membrane differs due to genetic characteristics. In this regard, the study of genetically determined changes in the expression of the functional activity of CYP family isoenzymes is of great clinical importance in psychiatry and clinical pharmacology [5][6][7].…”

Section: Discussionmentioning

confidence: 99%

Clinical Case of a 36-Year-Old Man with Treatment-Resistant Paranoid Schizophrenia: Personalized Therapy Selection

Linova

Torgovtsev

Лиманкин

et al. 2022

jour

View full text Add to dashboard Cite

Schizophrenia is a common and socially significant mental disorder that requires longterm use of antipsychotics (APs). Long-term use of APs increases the risk of developing adverse drug reactions (ADRs) and/or therapeutic resistance in some patients. This may be due to a genetically determined impairment of APs metabolism by cytochrome P450 enzymes and of Aps transport across the blood-brain barrier (BBB) and the cell membrane of APs target neurons in the brain. Pharmacogenetic testing (PGx) is a method to identify a group of patients with a high risk of developing AP-induced ADRs. The aim of the case report is to present the experience of using PGx in a 36-year-old patient with treatment-resistant schizophrenia and a medical history of AP-induced ADRs.

show abstract

Section: Discussionmentioning

confidence: 99%

Pharmacogenetic Testing of Cytochrome P450 System Enzymes in the Therapy of Bipolar Affective Disorder

Khasanova

Насырова

2022

jour

View full text Add to dashboard Cite

Bipolar affective disorder (BPS) is a common and socially significant mental disorder that requires long-term use of psychotropic drugs (PDs). Long-term use of PDs increases the risk of developing adverse drug reactions (ADRs) and/or therapeutic resistance in some patients. This may be due to a genetically determined impairment of PDs metabolism by cytochrome P450 enzymes. Pharmacogenetic testing (PGx) is a method to identify a group of patients with a high risk of developing PDs -induced ADRs. Our experience of using PGx to search for low-functional and non-functional single nucleotide variants (SNVs) / polymorphisms of the CYP1A2, CYP2C8, CYP3A4, CYP3A5 and CYP2D6 genes encoding cytochrome P450 enzymes involved in PDs metabolism demonstrates the importance of this new personalized approach to the choice of PDs and its dosing in patients with pharmacogenetic profile poor metabolizer. The main purpose of the case report is to present the experience of using PGx in the therapy of dipolar affective disorder.

show abstract

Problems and prospects for the implementation of pharmacogenetic testing in real clinical practice in the Russian Federation

Cited by 10 publications

References 7 publications

Genetic Predictors of Antipsychotic Efflux Impairment via Blood-Brain Barrier: Role of Transport Proteins

Genetic Predictors of Antipsychotic Efflux Impairment via Blood-Brain Barrier: Role of Transport Proteins

Clinical Case of a 36-Year-Old Man with Treatment-Resistant Paranoid Schizophrenia: Personalized Therapy Selection

Pharmacogenetic Testing of Cytochrome P450 System Enzymes in the Therapy of Bipolar Affective Disorder

Contact Info

Product

Resources

About