Association of ANKK1 polymorphism with antipsychotic-induced hyperprolactinemia

Hum Psychopharmacol. 2020 Jul;35(4):e2737. doi: 10.1002/hup.2737. Epub 2020 May 8.

Abstract

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 χ2 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 (χ2 = 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.

Keywords: ANKK1; hyperprolactinemia; polymorphism; schizophrenia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antipsychotic Agents / administration & dosage
  • Antipsychotic Agents / adverse effects*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Hyperprolactinemia / chemically induced*
  • Hyperprolactinemia / genetics
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Protein Serine-Threonine Kinases / genetics*
  • Receptors, Dopamine D2 / genetics
  • Schizophrenia / drug therapy*
  • Siberia

Substances

  • Antipsychotic Agents
  • DRD2 protein, human
  • Receptors, Dopamine D2
  • ANKK1 protein, human
  • Protein Serine-Threonine Kinases