title: Association study indicates a protective role of phosphatidylinositol-4-phosphate-5-kinase against tardive dyskinesia.
abstract: BACKGROUND
  Tardive dyskinesia is a disorder characterized by involuntary muscle movements that occur as a complication of long-term treatment with antipsychotic drugs. It has been suggested to be related to a malfunctioning of the indirect pathway of the motor part of the cortical-striatal-thalamic-cortical circuit, which may be caused by oxidative stress-induced neurotoxicity.
  
  
  METHODS
  The purpose of our study was to investigate the possible association between phosphatidylinositol-4-phosphate-5-kinase type IIa (PIP5K2A) function and tardive dyskinesia in 491 Caucasian patients with schizophrenia from 3 different psychiatric institutes in West Siberia. The Abnormal Involuntary Movement Scale was used to assess tardive dyskinesia. Individuals were genotyped for 3 single nucleotide polymorphisms in PIP5K2A gene: rs10828317, rs746203, and rs8341.
  
  
  RESULTS
  A significant association was established between the functional mutation N251S-polymorphism of the PIP5K2A gene (rs10828317) and tardive dyskinesia, while the other 2 examined nonfunctional single nucleotide polymorphisms were not related.
  
  
  CONCLUSIONS
  We conclude from this association that PIP5K2A is possibly involved in a mechanism protecting against tardive dyskinesia-inducing neurotoxicity. This corresponds to our hypothesis that tardive dyskinesia is related to neurotoxicity at striatal indirect pathway medium-sized spiny neurons.
authors.affiliation: Mental Health Research Institute, SiberianBranch of RAMSc, Tomsk, Siberia, Russian Federation (Drs Fedorenko, Toshchakova, Boyarko, Semke, Bokhan, and Ivanova); National Research Tomsk Polytechnic University, Tomsk, Siberia, Russian Federation (Drs Fedorenko and Ivanova); Department of Pharmacy, University of Groningen, Groningen, The Netherlands (Dr Loonen); Mental Health Institute Westelijk Noord-Brabant, Halsteren, The Netherlands (Dr Loonen); Department of Physiology, University of Tuebingen, Tuebingen, Germany (Dr Lang); Chita State Medical Academy, Chita, Siberia, Russian Federation (Dr Govorin); National Research Tomsk State University, Tomsk, Siberia, Russian Federation (Dr Bokhan); Scientific Research Institute of Physiology and Basic Medicine, Siberian Branch of RAMSc, Novosibirsk, Siberia, Russian Federation (Dr Aftanas).
authors.forename: Olga Yu
authors.initials: OY
authors.lastname: Fedorenko
authors.affiliation: Mental Health Research Institute, SiberianBranch of RAMSc, Tomsk, Siberia, Russian Federation (Drs Fedorenko, Toshchakova, Boyarko, Semke, Bokhan, and Ivanova); National Research Tomsk Polytechnic University, Tomsk, Siberia, Russian Federation (Drs Fedorenko and Ivanova); Department of Pharmacy, University of Groningen, Groningen, The Netherlands (Dr Loonen); Mental Health Institute Westelijk Noord-Brabant, Halsteren, The Netherlands (Dr Loonen); Department of Physiology, University of Tuebingen, Tuebingen, Germany (Dr Lang); Chita State Medical Academy, Chita, Siberia, Russian Federation (Dr Govorin); National Research Tomsk State University, Tomsk, Siberia, Russian Federation (Dr Bokhan); Scientific Research Institute of Physiology and Basic Medicine, Siberian Branch of RAMSc, Novosibirsk, Siberia, Russian Federation (Dr Aftanas). a.j.m.loonen@rug.nl.
authors.forename: Anton J M
authors.initials: AJ
authors.lastname: Loonen
authors.affiliation: Mental Health Research Institute, SiberianBranch of RAMSc, Tomsk, Siberia, Russian Federation (Drs Fedorenko, Toshchakova, Boyarko, Semke, Bokhan, and Ivanova); National Research Tomsk Polytechnic University, Tomsk, Siberia, Russian Federation (Drs Fedorenko and Ivanova); Department of Pharmacy, University of Groningen, Groningen, The Netherlands (Dr Loonen); Mental Health Institute Westelijk Noord-Brabant, Halsteren, The Netherlands (Dr Loonen); Department of Physiology, University of Tuebingen, Tuebingen, Germany (Dr Lang); Chita State Medical Academy, Chita, Siberia, Russian Federation (Dr Govorin); National Research Tomsk State University, Tomsk, Siberia, Russian Federation (Dr Bokhan); Scientific Research Institute of Physiology and Basic Medicine, Siberian Branch of RAMSc, Novosibirsk, Siberia, Russian Federation (Dr Aftanas).
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
authors.affiliation: Mental Health Research Institute, SiberianBranch of RAMSc, Tomsk, Siberia, Russian Federation (Drs Fedorenko, Toshchakova, Boyarko, Semke, Bokhan, and Ivanova); National Research Tomsk Polytechnic University, Tomsk, Siberia, Russian Federation (Drs Fedorenko and Ivanova); Department of Pharmacy, University of Groningen, Groningen, The Netherlands (Dr Loonen); Mental Health Institute Westelijk Noord-Brabant, Halsteren, The Netherlands (Dr Loonen); Department of Physiology, University of Tuebingen, Tuebingen, Germany (Dr Lang); Chita State Medical Academy, Chita, Siberia, Russian Federation (Dr Govorin); National Research Tomsk State University, Tomsk, Siberia, Russian Federation (Dr Bokhan); Scientific Research Institute of Physiology and Basic Medicine, Siberian Branch of RAMSc, Novosibirsk, Siberia, Russian Federation (Dr Aftanas).
authors.forename: Valentina A
authors.initials: VA
authors.lastname: Toshchakova
authors.affiliation: Mental Health Research Institute, SiberianBranch of RAMSc, Tomsk, Siberia, Russian Federation (Drs Fedorenko, Toshchakova, Boyarko, Semke, Bokhan, and Ivanova); National Research Tomsk Polytechnic University, Tomsk, Siberia, Russian Federation (Drs Fedorenko and Ivanova); Department of Pharmacy, University of Groningen, Groningen, The Netherlands (Dr Loonen); Mental Health Institute Westelijk Noord-Brabant, Halsteren, The Netherlands (Dr Loonen); Department of Physiology, University of Tuebingen, Tuebingen, Germany (Dr Lang); Chita State Medical Academy, Chita, Siberia, Russian Federation (Dr Govorin); National Research Tomsk State University, Tomsk, Siberia, Russian Federation (Dr Bokhan); Scientific Research Institute of Physiology and Basic Medicine, Siberian Branch of RAMSc, Novosibirsk, Siberia, Russian Federation (Dr Aftanas).
authors.forename: Evgenia G
authors.initials: EG
authors.lastname: Boyarko
authors.affiliation: Mental Health Research Institute, SiberianBranch of RAMSc, Tomsk, Siberia, Russian Federation (Drs Fedorenko, Toshchakova, Boyarko, Semke, Bokhan, and Ivanova); National Research Tomsk Polytechnic University, Tomsk, Siberia, Russian Federation (Drs Fedorenko and Ivanova); Department of Pharmacy, University of Groningen, Groningen, The Netherlands (Dr Loonen); Mental Health Institute Westelijk Noord-Brabant, Halsteren, The Netherlands (Dr Loonen); Department of Physiology, University of Tuebingen, Tuebingen, Germany (Dr Lang); Chita State Medical Academy, Chita, Siberia, Russian Federation (Dr Govorin); National Research Tomsk State University, Tomsk, Siberia, Russian Federation (Dr Bokhan); Scientific Research Institute of Physiology and Basic Medicine, Siberian Branch of RAMSc, Novosibirsk, Siberia, Russian Federation (Dr Aftanas).
authors.forename: Arkadiy V
authors.initials: AV
authors.lastname: Semke
authors.affiliation: Mental Health Research Institute, SiberianBranch of RAMSc, Tomsk, Siberia, Russian Federation (Drs Fedorenko, Toshchakova, Boyarko, Semke, Bokhan, and Ivanova); National Research Tomsk Polytechnic University, Tomsk, Siberia, Russian Federation (Drs Fedorenko and Ivanova); Department of Pharmacy, University of Groningen, Groningen, The Netherlands (Dr Loonen); Mental Health Institute Westelijk Noord-Brabant, Halsteren, The Netherlands (Dr Loonen); Department of Physiology, University of Tuebingen, Tuebingen, Germany (Dr Lang); Chita State Medical Academy, Chita, Siberia, Russian Federation (Dr Govorin); National Research Tomsk State University, Tomsk, Siberia, Russian Federation (Dr Bokhan); Scientific Research Institute of Physiology and Basic Medicine, Siberian Branch of RAMSc, Novosibirsk, Siberia, Russian Federation (Dr Aftanas).
authors.forename: Nikolay A
authors.initials: NA
authors.lastname: Bokhan
authors.affiliation: Mental Health Research Institute, SiberianBranch of RAMSc, Tomsk, Siberia, Russian Federation (Drs Fedorenko, Toshchakova, Boyarko, Semke, Bokhan, and Ivanova); National Research Tomsk Polytechnic University, Tomsk, Siberia, Russian Federation (Drs Fedorenko and Ivanova); Department of Pharmacy, University of Groningen, Groningen, The Netherlands (Dr Loonen); Mental Health Institute Westelijk Noord-Brabant, Halsteren, The Netherlands (Dr Loonen); Department of Physiology, University of Tuebingen, Tuebingen, Germany (Dr Lang); Chita State Medical Academy, Chita, Siberia, Russian Federation (Dr Govorin); National Research Tomsk State University, Tomsk, Siberia, Russian Federation (Dr Bokhan); Scientific Research Institute of Physiology and Basic Medicine, Siberian Branch of RAMSc, Novosibirsk, Siberia, Russian Federation (Dr Aftanas).
authors.forename: Nikolay V
authors.initials: NV
authors.lastname: Govorin
authors.affiliation: Mental Health Research Institute, SiberianBranch of RAMSc, Tomsk, Siberia, Russian Federation (Drs Fedorenko, Toshchakova, Boyarko, Semke, Bokhan, and Ivanova); National Research Tomsk Polytechnic University, Tomsk, Siberia, Russian Federation (Drs Fedorenko and Ivanova); Department of Pharmacy, University of Groningen, Groningen, The Netherlands (Dr Loonen); Mental Health Institute Westelijk Noord-Brabant, Halsteren, The Netherlands (Dr Loonen); Department of Physiology, University of Tuebingen, Tuebingen, Germany (Dr Lang); Chita State Medical Academy, Chita, Siberia, Russian Federation (Dr Govorin); National Research Tomsk State University, Tomsk, Siberia, Russian Federation (Dr Bokhan); Scientific Research Institute of Physiology and Basic Medicine, Siberian Branch of RAMSc, Novosibirsk, Siberia, Russian Federation (Dr Aftanas).
authors.forename: Lyubomir I
authors.initials: LI
authors.lastname: Aftanas
authors.affiliation: Mental Health Research Institute, SiberianBranch of RAMSc, Tomsk, Siberia, Russian Federation (Drs Fedorenko, Toshchakova, Boyarko, Semke, Bokhan, and Ivanova); National Research Tomsk Polytechnic University, Tomsk, Siberia, Russian Federation (Drs Fedorenko and Ivanova); Department of Pharmacy, University of Groningen, Groningen, The Netherlands (Dr Loonen); Mental Health Institute Westelijk Noord-Brabant, Halsteren, The Netherlands (Dr Loonen); Department of Physiology, University of Tuebingen, Tuebingen, Germany (Dr Lang); Chita State Medical Academy, Chita, Siberia, Russian Federation (Dr Govorin); National Research Tomsk State University, Tomsk, Siberia, Russian Federation (Dr Bokhan); Scientific Research Institute of Physiology and Basic Medicine, Siberian Branch of RAMSc, Novosibirsk, Siberia, Russian Federation (Dr Aftanas).
authors.forename: Svetlana A
authors.initials: SA
authors.lastname: Ivanova
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects*; D004409:Dyskinesia, Drug-Induced / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics* / Q000517:prevention & control; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009069:Movement Disorders / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics* / Q000517:prevention & control; D010641:Phenotype; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D065840:Protective Factors; D018570:Risk Assessment; D012307:Risk Factors; D012559:Schizophrenia / Q000188:drug therapy*; D012800:Siberia; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; C514871:PIP4K2A protein, human; D017853:Phosphotransferases (Alcohol Group Acceptor)
keywords: PIP5K2A; gene polymorphism; medium spiny neurons; neurotoxicity; schizophrenia; tardive dyskinesia