Abstract
ObjectiveSchizophrenia 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.MethodsWe 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 χ2 test.ResultsA 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 (χ2 = 3.70; p = .05; odds ratio [OR] = 1.30 [0.99–1.69]).ConclusionThe functional polymorphism rs2734849 in the ANKK1 gene was associated with HPRL in patients with schizophrenia.
Highlights
Schizophrenia is a severe mental disorder characterized by disruptions in thought processes, perceptions, volition, emotional responsiveness, cognitive processes, and social interactions
Since genetic variation in gene coding for proteins that cross-talk with Dopamine Receptor D2 type (DRD2) at the molecular level are associated with response to antipsychotics (Rampino et al, 2019), the ANKK1 gene (Ankyrin Repeat and Kinase Domain containing 1) is of particular interest
Since dopamine inhibits prolactin secretion by binding to D2 receptors expressed on the cell membrane of the anterior pituitary lactotrophs, we hypothesized that ANKK1 polymorphism modulation of DRD2 expression can be involved in the mechanisms of HPRL induced by antipsychotics due to their high affinity for the D2 receptor
Summary
Schizophrenia is a severe mental disorder characterized by disruptions in thought processes, perceptions, volition, emotional responsiveness, cognitive processes, and social interactions. Since genetic variation in gene coding for proteins that cross-talk with DRD2 at the molecular level are associated with response to antipsychotics (Rampino et al, 2019), the ANKK1 gene (Ankyrin Repeat and Kinase Domain containing 1) is of particular interest. The exact role of SNP rs2734849 in ANKK1 in psychiatric disorders and drug-induced side effects has yet to be fully characterized. Since dopamine inhibits prolactin secretion by binding to D2 receptors expressed on the cell membrane of the anterior pituitary lactotrophs, we hypothesized that ANKK1 polymorphism modulation of DRD2 expression can be involved in the mechanisms of HPRL induced by antipsychotics due to their high affinity for the D2 receptor. In this study we investigated the association of ANKK1 rs2734849 polymorphism with antipsychotic-induced HPRL in Russian patients with schizophrenia
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