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

Diana Z. Osmanova, Maxim B. Freidin, Olga Yu Fedorenko, Ivan V. Pozhidaev, Anastasiia S. Boiko, Natalia M. Vyalova, Vladimir V. Tiguntsev, Elena G. Kornetova, Anton J.M. Loonen, Arkadiy V. Semke, Bob Wilffert, Nikolay A. Bokhan, Svetlana A. Ivanova

Результат исследований: Материалы для журналаСтатья

1 цитирование (Scopus)

Выдержка

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.

Язык оригиналаАнглийский
Номер статьи47
ЖурналBMC Medical Genetics
Том20
DOI
СостояниеОпубликовано - 9 апр 2019

Отпечаток

Siberia
Hyperprolactinemia
Antipsychotic Agents
Schizophrenia
Risperidone
Lactotrophs
Dopamine Plasma Membrane Transport Proteins
Dopamine Receptors
Prolactin
Genes
Dopamine
Pharmacogenomic Testing
Anterior Pituitary Gland
Dopamine D2 Receptors
Genetic Models
International Classification of Diseases
Pituitary Gland
Enzymes
Drug-Related Side Effects and Adverse Reactions
Genetic Markers

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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A pharmacogenetic study of patients with schizophrenia from West Siberia gets insight into dopaminergic mechanisms of antipsychotic-induced hyperprolactinemia. / Osmanova, Diana Z.; Freidin, Maxim B.; Fedorenko, Olga Yu; Pozhidaev, Ivan V.; Boiko, Anastasiia S.; Vyalova, Natalia M.; Tiguntsev, Vladimir V.; Kornetova, Elena G.; Loonen, Anton J.M.; Semke, Arkadiy V.; Wilffert, Bob; Bokhan, Nikolay A.; Ivanova, Svetlana A.

В: BMC Medical Genetics, Том 20, 47, 09.04.2019.

Результат исследований: Материалы для журналаСтатья

Osmanova, DZ, Freidin, MB, Fedorenko, OY, Pozhidaev, IV, Boiko, AS, Vyalova, NM, Tiguntsev, VV, Kornetova, EG, Loonen, AJM, Semke, AV, Wilffert, B, Bokhan, NA & Ivanova, SA 2019, 'A pharmacogenetic study of patients with schizophrenia from West Siberia gets insight into dopaminergic mechanisms of antipsychotic-induced hyperprolactinemia', BMC Medical Genetics, том. 20, 47. https://doi.org/10.1186/s12881-019-0773-3
Osmanova, Diana Z. ; Freidin, Maxim B. ; Fedorenko, Olga Yu ; Pozhidaev, Ivan V. ; Boiko, Anastasiia S. ; Vyalova, Natalia M. ; Tiguntsev, Vladimir V. ; Kornetova, Elena G. ; Loonen, Anton J.M. ; Semke, Arkadiy V. ; Wilffert, Bob ; Bokhan, Nikolay A. ; Ivanova, Svetlana A. / A pharmacogenetic study of patients with schizophrenia from West Siberia gets insight into dopaminergic mechanisms of antipsychotic-induced hyperprolactinemia. В: BMC Medical Genetics. 2019 ; Том 20.
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title = "A pharmacogenetic study of patients with schizophrenia from West Siberia gets insight into dopaminergic mechanisms of antipsychotic-induced hyperprolactinemia",
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.",
keywords = "Antipsychotics, Dopamine receptors genes, Dopamine transporter SLC6A3, Hyperprolactinemia, Monoamine oxidase (MAO)",
author = "Osmanova, {Diana Z.} and Freidin, {Maxim B.} and Fedorenko, {Olga Yu} and Pozhidaev, {Ivan V.} and Boiko, {Anastasiia S.} and Vyalova, {Natalia M.} and Tiguntsev, {Vladimir V.} and Kornetova, {Elena G.} and Loonen, {Anton J.M.} and Semke, {Arkadiy V.} and Bob Wilffert and Bokhan, {Nikolay A.} and Ivanova, {Svetlana A.}",
year = "2019",
month = "4",
day = "9",
doi = "10.1186/s12881-019-0773-3",
language = "English",
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journal = "BMC Medical Genetics",
issn = "1471-2350",
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TY - JOUR

T1 - A pharmacogenetic study of patients with schizophrenia from West Siberia gets insight into dopaminergic mechanisms of antipsychotic-induced hyperprolactinemia

AU - Osmanova, Diana Z.

AU - Freidin, Maxim B.

AU - Fedorenko, Olga Yu

AU - Pozhidaev, Ivan V.

AU - Boiko, Anastasiia S.

AU - Vyalova, Natalia M.

AU - Tiguntsev, Vladimir V.

AU - Kornetova, Elena G.

AU - Loonen, Anton J.M.

AU - Semke, Arkadiy V.

AU - Wilffert, Bob

AU - Bokhan, Nikolay A.

AU - Ivanova, Svetlana A.

PY - 2019/4/9

Y1 - 2019/4/9

N2 - 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.

AB - 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.

KW - Antipsychotics

KW - Dopamine receptors genes

KW - Dopamine transporter SLC6A3

KW - Hyperprolactinemia

KW - Monoamine oxidase (MAO)

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U2 - 10.1186/s12881-019-0773-3

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