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Association of polymorphism in the dopamine receptors and transporter genes with hyperprolactinemia in patients with schizophrenia

Osmanova, D., Boiko, A. S., Fedorenko, O. Y., Pozhidaev, I. V., Freidin, M. B., Kornetova, E. G., Ivanova, S. A., Wilffert, B. & Loonen, A. J. M., 4-Oct-2017, In : European Neuropsychopharmacology. 27, Suppl. 4, p. 923-924 2 p.

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  • Association of polymorphism in the dopamine receptors and transporter genes with hyperprolactinemia in patients with schizophrenia

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  • D. Osmanova
  • A.S. Boiko
  • O.Y. Fedorenko
  • I.V. Pozhidaev
  • M.B. Freidin
  • E.G. Kornetova
  • S.A. Ivanova
  • B. Wilffert
  • A.J.M. Loonen
Background: Long-term antipsychotic drug use remains the mainstay of treatment for patients with schizophrenia. However, pharmacotherapy with these drugs is complicated by several troublesome side effects, including hyperprolactinemia (HP). Prolactin secretion is persistently inhibited by dopamine, and antipsychotic drugs are believed to increase prolactin release by blocking dopamine receptors in the pituitary gland. Genetic factors play an important role in the development of antipsychotic induced HP [1, 2]. Genes coding for dopamine receptors and transporters are considered to be responsible for HP in schizophrenia [3]. The present study aimed to investigate the role of polymorph-isms of the dopamine receptors and transporters genes (DRD1, DRD2, SLC6A3) in the pathogenesis of antipsychotic-related HP in patients with schizophrenia. Methods: 431 Russian patients with schizophrenia were examined. The average age of patients was 42.1 ± 1.4 years. Evaluation of serum prolactin level was performed by ELISA using reagents set PRL Test System (USA). Genotyping was carried out on 17 polymorphic variants of the dopamine receptors and transporters genes DRD1 (rs4532, rs936461), DRD2 (rs4245147, rs6279, rs2734842) and SLC6A3 (rs3756450, rs2550956, rs6347, rs2617605, rs3863145, rs250686, rs464049, rs4975646, rs1048953, rs11133767, rs27048, rs40184). The SPSS sof tware was used for statistical analysis. The Hardy-Weinberg equilibrium (HWE) of genotypic frequencies was tested by the chi-square test. Results: We studied the association between HP and a set of SNPs from DRD1, DRD2 receptor genes and neurotransmitter transporter SLC6A3 in patients from Siberia with a clinical diagnosis of schizophrenia who were treated with classical and/or atypical antipsychotic drugs. All patients with schizophrenia were divided into two groups: those with and without HP. Physiological normal results for the serum prolactin levels are less than 20 ng/ml in men, and less than 25 ng/ml in women. Statistically significant result was obtained for polymorphic variant rs2550956 of the gene SLC6A3 (χ2 = 9.992; p = 0.007), which suggests its involvement in the development of HP. The heterozygous genotype TC of rs2550956 was significantly less common in patients with elevated levels of prolactin and it presumably has protective properties (OR 0.54; 95% CI: 0.36-0.81). We did not find any statistically significant associations for other polymorphisms DRD1 (rs4532, rs936461), DRD2 (rs4245147, rs6279, rs2734842) and SLC6A3 (rs3756450, rs6347, rs2617605, rs3863145, rs250686, rs464049, rs4975646, rs1048953, rs11133767, rs27048, rs40184). The group of dopamine receptors is heterogeneous and only some of them participate in the formation of psychotic symptoms and, accord ingly, in the antipsychotic action of neuroleptics. The effect of neuroleptics on other groups of dopamine receptors leads to the development of different side effects including extrapyramidal disorders [4], and their role is extremely low in the formation of the actual therapeutic response. Conclusion: Our results indicate that genetic variants of SLC6A3 may have functional consequences on the modulation of prolactin secretion. Neurotransmitter systems are involved in the mechanisms of action of antipsychotic drugs; therefore, a further search for genetic markers associated with the development of antipsychotic-related hyperprolactinemia in schizophrenic patients is needed.
Original languageEnglish
Pages (from-to)923-924
Number of pages2
JournalEuropean Neuropsychopharmacology
Volume27
Issue numberSuppl. 4
Publication statusPublished - 4-Oct-2017

    Keywords

  • atypical antipsychotic agent, dopamine 1 receptor, dopamine 2 receptor, dopamine transporter, endogenous compound, neurotransmitter, neurotransmitter transporter, prolactin, adult, chi square test, clinical trial, controlled clinical trial, controlled study, data analysis software, diagnosis, DNA polymorphism, drug therapy, enzyme linked immunosorbent assay, extrapyramidal syndrome, female, gene expression, gene frequency, gene mutation, genetic marker, genetic variability, heterozygosity, human, hyperprolactinemia, major clinical study, male, modulation, prolactin blood level, prolactin release, psychosis, receptor gene, Russian (citizen), side effect, treatment response

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