Diana Z Osmanova1,2, Maxim B Freidin3,4, Olga Yu Fedorenko1,5, Ivan V Pozhidaev1,2, Anastasiia S Boiko1, Natalia M Vyalova1, Vladimir V Tiguntsev1, Elena G Kornetova1, Anton J M Loonen6,7, Arkadiy V Semke1, Bob Wilffert6,8, Nikolay A Bokhan1,2, Svetlana A Ivanova9,10. 1. Mental Health Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, Aleutskaya str., 4, Tomsk, Russian Federation, 634014. 2. National Research Tomsk State University, Lenin Avenue, Tomsk, Russian Federation, 36. 3. Department of Twin Research and Genetic Epidemiology, School of Live Course Sciences, King's College London, Lambeth Palace Road, London, SE1 7EH, UK. 4. Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences, Naberezhnaya Ushaiki str, Tomsk, Russian Federation, 10. 5. National Research Tomsk Polytechnic University, Lenin Avenue, Tomsk, Russian Federation, 30. 6. Groningen Research Institute of Pharmacy, PharmacoTherapy, Epidemiology & Economics, University of Groningen, Antonius Deusinglaan 1, 9713, AV, Groningen, The Netherlands. 7. GGZ Westelijk Noord-Brabant, Hoofdlaan 8, 4661 AA, Halsteren, The Netherlands. 8. University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, University of Groningen, Hanzeplein 1, 9713, GZ, Groningen, The Netherlands. 9. Mental Health Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, Aleutskaya str., 4, Tomsk, Russian Federation, 634014. ivanovaniipz@gmail.com. 10. National Research Tomsk Polytechnic University, Lenin Avenue, Tomsk, Russian Federation, 30. ivanovaniipz@gmail.com.
Abstract
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.
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 transporterSLC6A3 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 schizophrenicpatients is needed.
Authors: Olga Yu Fedorenko; Diana Z Paderina; Anton J M Loonen; Ivan V Pozhidaev; Anastasiia S Boiko; Elena G Kornetova; Nikolay A Bokhan; Bob Wilffert; Svetlana A Ivanova Journal: Hum Psychopharmacol Date: 2020-05-08 Impact factor: 1.672
Authors: Diana Z Paderina; Anastasiia S Boiko; Ivan V Pozhidaev; Irina A Mednova; Anastasia A Goncharova; Anna V Bocharova; Olga Yu Fedorenko; Elena G Kornetova; Arkadiy V Semke; Nikolay A Bokhan; Anton J M Loonen; Svetlana A Ivanova Journal: Genes (Basel) Date: 2022-07-23 Impact factor: 4.141