Identification of 5-hydroxytryptamine receptor gene polymorphisms modulating hyperprolactinaemia in antipsychotic drug-treated patients with schizophrenia

Ivanova, Svetlana A.; Osmanova, D.; Freidin, Maxim B.; Fedorenko, Olga Yu; Boiko, Anastasiia S.; Pozhidaev, Ivan V; Semke, A.; Бохан, Н. А.; Agarkov, Alexey; Wilffert, Bob; Loonen, Anton J. M.

doi:10.1080/15622975.2016.1224926

Cited by 28 publications

(25 citation statements)

References 39 publications

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“…In a previous study, none of the studied HTR2A and HTR2C polymorphisms were associated with antipsychotic‐induced hyperprolactinaemia. However, a tendency of association was found between HTR2C rs3813929 and prolactin levels when treated with several antipsychotic drugs . In the current study, volunteers carrying the HTR2C rs3813929 C/C genotype had significantly lower prolactin AUC 0‐12 and C max levels than T allele carriers, suggesting a lower HTR2C occupancy than individuals carrying the T allele.…”

Section: Discussioncontrasting

confidence: 47%

“…HTR2A and HTR2C polymorphisms were analysed related to hyperprolactinaemia in schizophrenic patients treated with classical and/or atypical antipsychotic drugs in a previous study: they found no association between HTR2A polymorphisms and hyperprolactinaemia. However, a significant association was established in case of various HTR2C polymorphisms . Nevertheless, prolactin concentrations in schizophrenic patients after ARI administration were not affected by DRD2 rs1800497, rs6277 polymorphisms and CYP2D6 phenotype …”

Section: Introductionmentioning

confidence: 91%

“…However, a significant association was established in case of various HTR2C polymorphisms. 15 Nevertheless, prolactin concentrations in schizophrenic patients after ARI administration were not affected by DRD2 rs1800497, rs6277 polymorphisms and CYP2D6 phenotype. 11 The aim of the current study was to evaluate the effect of a single dose of ARI on circadian prolactin secretion and its correlation with various factors including sex, plasma drug concentrations and selected genetic polymorphisms in DRD2, DRD3, HTR2A, HTR2C and CYP2D6 genes.…”

Section: Introductionmentioning

confidence: 93%

“…However, ARI is a partial D2 receptor agonist and therefore provides sufficient dopaminergic tone to continue inhibition of prolactin release . Even though dopamine is considered as the primary factor inhibiting prolactin release, the activity of prolactin‐producing lactotrophs is also regulated by 5‐HT . However, the involvement of 5‐HT receptors HTR1A, HTR2A, HTR2C and HTR3 in serotonergic‐induced prolactin response is still unclear…”

Section: Introductionmentioning

confidence: 99%

“…14 Even though dopamine is considered as the primary factor inhibiting prolactin release, the activity of prolactin-producing lactotrophs is also regulated by 5-HT. 15 However, the involvement of 5-HT receptors HTR1A, HTR2A, HTR2C and HTR3 in serotonergic-induced prolactin response is still unclear. 16 Dopamine D2 receptor (DRD2) gene polymorphisms were associated with prolactin release modulation in healthy volunteers after olanzapine and risperidone administration, but not quetiapine.…”

Section: Introductionmentioning

confidence: 99%

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Effects of aripiprazole on circadian prolactin secretion related to pharmacogenetics in healthy volunteers

Koller

Belmonte

Saiz‐Rodríguez

et al. 2019

Basic Clin Pharma Tox

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Aripiprazole treatment in schizophrenic patients was previously associated with lower or normalized prolactin levels. Genetic variants in cytochrome P450 (CYP) (CYP2D6), dopamine receptor (DRD2, DRD3) and serotonin receptor (HTR2A, HTR2C) genes were previously associated with antipsychotic‐induced hyperprolactinaemia. Our aim was to evaluate whether aripiprazole affects prolactin secretion and its relationship with pharmacogenetics. Thirty‐one healthy volunteers receiving a 10‐mg single oral dose of aripiprazole were genotyped for 12 polymorphisms in CYP2D6, DRD2, DRD3, HTR2A and HTR2C genes by qPCR. Aripiprazole and dehydro‐aripiprazole plasma concentrations were measured by HPLC‐MS/MS. Prolactin concentrations of the 31 volunteers taking aripiprazole and 12 volunteers receiving ibuprofen were determined by ELISA. Prolactin concentrations after ibuprofen intake were considered as control, since it is known to cause no effect. Prolactin concentrations were slightly higher in the aripiprazole group compared to the ibuprofen group. All prolactin pharmacokinetic parameters were higher in females than in males. CYP2D6 poor and intermediate metabolizers had notably higher prolactin Cmax and AUC0‐12 than normal and ultrarapid metabolizers. The DRD3 rs6280 polymorphism affected prolactin levels: volunteers carrying Ser/Ser genotype had significantly lower prolactin levels than volunteers carrying the Gly allele. Furthermore, HTR2C rs3813929 C/C homozygotes had significantly lower prolactin levels than T allele carriers. Nevertheless, aripiprazole did increase prolactin levels compared to ibuprofen.

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Section: Discussioncontrasting

confidence: 47%

Section: Introductionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Effects of aripiprazole on circadian prolactin secretion related to pharmacogenetics in healthy volunteers

Koller

Belmonte

Saiz‐Rodríguez

et al. 2019

Basic Clin Pharma Tox

View full text Add to dashboard Cite

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Genetic variability of serotonin pathway associated with schizophrenia onset, progression, and treatment

Hrovatin

Kunej

Dolžan

2019

American J of Med Genetics Pt B

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Schizophrenia (SZ) onset and treatment outcome have important genetic components, however individual genes do not have strong effects on SZ phenotype. Therefore, it is important to use the pathway-based approach and study metabolic and signaling pathways, such as dopaminergic and serotonergic. Serotonin pathway has an important role in brain signaling, nevertheless, its role in SZ is not as thoroughly examined as that of dopamine pathway. In this study, we reviewed serotonin pathway genes and genetic variations associated with SZ, including variations at DNA, RNA, and epigenetic level.We obtained 30 serotonin pathway genes from Kyoto encyclopedia of genes and genomes and used these genes for the literature review. We extracted 20 protein coding serotonin pathway genes with genetic variations associated with SZ onset, development, and treatment from 31 research papers. Genes associated with SZ are present on all levels of serotonin pathway: serotonin synthesis, transport, receptor binding, intracellular signaling, and reuptake; however, regulatory genes are poorly researched. We summarized common challenges of genetic association studies and presented some solutions. The analysis of reported serotonin pathway-SZ associations revealed lack of information about certain serotonin pathway genes potentially associated with SZ. Furthermore, it is becoming clear that interactions among serotonin pathway genes and their regulators may bring further knowledge about their involvement in SZ. K E Y W O R D Sgenetic association studies, genetic variations, pharamcogenetics, schizophrenia, serotonin pathway

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Association of ANKK1 polymorphism with antipsychotic‐induced hyperprolactinemia

Fedorenko

Paderina

Loonen

et al. 2020

Human Psychopharmacology

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Objective Schizophrenia is a severe highly heritable mental disorder. Genetic polymorphisms of dopaminergic pathways are related to pathogenesis of drug response. Hyperprolactinemia (HPRL), a common adverse effect of antipsychotics, is attributed to blockade of dopamine D2 receptors. Ankyrin Repeat and Kinase Domain containing 1 ( ANKK1 ) gene is closely related to Dopamine Receptor D2 type ( DRD2 ) gene functioning. We examined whether the functional polymorphism rs2734849 in the ANKK1 gene is associated with antipsychotic‐induced HPRL. Methods We recruited 446 patients with schizophrenia from among the Russian population of the Siberian region. The polymorphism rs2734849 in the ANKK1 gene was genotyped with The MassARRAY® Analyzer 4 by Agena Bioscience™, using the kit SEQUENOM Consumables iPLEXGold 384. Genotype and allele frequencies were compared between groups of schizophrenia patients with and without HPRL using the χ 2 test. Results A comparison between schizophrenia patients with and without HPRL revealed significantly higher frequency of the C allele of the polymorphic variant rs2734849 in the ANKK1 gene in patients with HPRL as compared to the patients without it (χ 2 = 3.70; p = .05; odds ratio [OR] = 1.30 [0.99–1.69]). Conclusion The functional polymorphism rs2734849 in the ANKK1 gene was associated with HPRL in patients with schizophrenia.

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Identification of 5-hydroxytryptamine receptor gene polymorphisms modulating hyperprolactinaemia in antipsychotic drug-treated patients with schizophrenia

Cited by 28 publications

References 39 publications

Effects of aripiprazole on circadian prolactin secretion related to pharmacogenetics in healthy volunteers

Effects of aripiprazole on circadian prolactin secretion related to pharmacogenetics in healthy volunteers

Genetic variability of serotonin pathway associated with schizophrenia onset, progression, and treatment

Association of ANKK1 polymorphism with antipsychotic‐induced hyperprolactinemia

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