A pharmacogenetic study of patients with schizophrenia from West Siberia gets insight into dopaminergic mechanisms of antipsychotic-induced hyperprolactinemia

Autor: Arkadiy V. Semke, Diana Z Osmanova, Bob Wilffert, Maxim B. Freidin, Olga Yu Fedorenko, Svetlana A. Ivanova, Vladimir V Tiguntsev, Elena G Kornetova, Anton J. M. Loonen, Nikolay A. Bokhan, Ivan V Pozhidaev, N. Vyalova, Anastasiia S Boiko
Přispěvatelé: PharmacoTherapy, -Epidemiology and -Economics, Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET)
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Adult
Male
0301 basic medicine
lcsh:Internal medicine
medicine.medical_specialty
lcsh:QH426-470
medicine.drug_class
Dopamine
Atypical antipsychotic
030105 genetics & heredity
Polymorphism
Single Nucleotide
Receptors
Dopamine
03 medical and health sciences
Internal medicine
Dopamine receptor D2
Genetic model
Genetics
Antipsychotics
Humans
Medicine
Paliperidone
lcsh:RC31-1245
Genetics (clinical)
Dopamine transporter
Dopamine Plasma Membrane Transport Proteins
Risperidone
biology
business.industry
Research
Dopamine transporter SLC6A3
Middle Aged
Dopamine receptors genes
Pharmacogenomic Testing
Hyperprolactinemia
Siberia
lcsh:Genetics
030104 developmental biology
Endocrinology
Dopamine receptor
Schizophrenia
biology.protein
Female
Monoamine oxidase (MAO)
business
Antipsychotic Agents
medicine.drug
Zdroj: BMC MEDICAL GENETICS, 20(Suppl 1). BMC
BMC Medical Genetics
BMC Medical Genetics, Vol 20, Iss S1, Pp 35-44 (2019)
Osmanova, D Z, Freidin, M B, Fedorenko, O Y, Pozhidaev, I V, Boiko, A S, Vyalova, N M, Tiguntsev, V V, Kornetova, E G, Loonen, A J M, Semke, A V, Wilffert, B, Bokhan, N A & Ivanova, S A 2019, ' A pharmacogenetic study of patients with schizophrenia from West Siberia gets insight into dopaminergic mechanisms of antipsychotic-induced hyperprolactinemia ', BMC Medical Genetics, vol. 20, no. Suppl 1, 47, pp. 47 . https://doi.org/10.1186/s12881-019-0773-3
ISSN: 1471-2350
DOI: 10.1186/s12881-019-0773-3
Popis: Background Hyperprolactinemia (HPRL) is a classical side effect of antipsychotic drugs primarily attributed to blockade of dopamine D2 receptors (DRD2s) on the membranes of lactotroph cells within the pituitary gland. Certain antipsychotic drugs, e.g. risperidone, are more likely to induce HPRL because of relative accumulation within the adenohypophysis. Nevertheless, due to competition for pituitary DRD2s by high dopamine levels may limit antipsychotic-induced HPRL. Moreover, the activity of prolactin-producing lactotrophs also depends on other hormones which are regulated by the extra-pituitary activity of dopamine receptors, dopamine transporters, enzymes of neurotransmitter metabolism and other factors. Polymorphic variants in the genes coding for these receptors and proteins can have functional significance and influence on the development of hyperprolactinemia. Methods A set of 41 SNPs of genes for dopamine receptors DRD1, DRD2, DRD3, DRD4, the dopamine transporter SLC6A3 and dopamine catabolizing enzymes MAOA and MAOB was investigated in a population of 446 Caucasians (221 males/225 females) with a clinical diagnosis of schizophrenia (according to ICD-10: F20) with and without HPRL who were treated with classical and/or atypical antipsychotic drugs. Additive genetic model was tested and the analysis was carried out in the total group and in subgroup stratified by the use of risperidone/paliperidone. Results One statistically significant association between polymorphic variant rs1799836 of MAOB gene and HPRL in men was found in the total group. Furthermore, the rs40184 and rs3863145 variants in SLC6A3 gene appeared to be associated with HPRL in the subgroup of patients using the risperidone/paliperidone, but not with HPRL induced by other antipsychotic drugs. Conclusions Our results indicate that genetic variants of MAOB and SLC6A3 may have consequences on the modulation of prolactin secretion. A further search for genetic markers associated with the development of antipsychotic-related hyperprolactinemia in schizophrenic patients is needed. Electronic supplementary material The online version of this article (10.1186/s12881-019-0773-3) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
Externí odkaz: