Association of ANKK1 polymorphism with antipsychotic-induced hyperprolactinemia

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 (R) Analyzer 4 by Agena Bioscience (TM), using the kit SEQUENOM Consumables iPLEXGold 384. Genotype and allele frequencies were compared between groups of schizophrenia patients with and without HPRL using the chi(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 (chi(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.