HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Association of the ZFPM2 gene with antipsychotic-induced parkinsonism in schizophrenia patients.

AbstractRATIONALE:
Antipsychotic-induced parkinsonism (AIP) is a severe adverse affect of antipsychotic drug treatment. Recently, our group performed a genome-wide association study (GWAS) for AIP severity, and identified several potential AIP risk variants.
OBJECTIVES:
The aim of this study was to validate our original AIP-GWAS susceptibility variants and to understand their possible function.
METHODS:
We conducted a validation study of 15 single-nucleotide polymorphisms (SNPs) in an independent sample of 178 US schizophrenia patients treated for at least a month with typical or atypical antipsychotics. Then, a sample of 49 Jewish Israeli Parkinson's disease (PD) patients with available neuroimaging ([(123)I]-FP-CIT-SPECT) data was analyzed, to study association of confirmed AIP SNPs with level of dopaminergic deficits in the putamen.
RESULTS:
Using logistic regression and controlling for possible confounders, we found nominal association of the intronic SNP, rs12678719, in the Zinc Finger Protein Multitype 2 (ZFPM2) gene with AIP (62 affected/116 unaffected), in the whole sample (p = 0.009; P = 5.97 × 10(-5) in the GWAS), and in the African American sub-sample (N = 111; p = 0.002). The same rs12678719-G AIP susceptibility allele was associated with lower levels of dopaminergic neuron related ligand binding in the contralateral putamen of PD patients (p = 0.026).
CONCLUSIONS:
Our preliminary findings support association of the ZFPM2 SNP, rs12678719, with AIP. At the functional level, this variant is associated with deficits in the nigrostriatal pathway in PD patients that may be related to latent subclinical deficits among AIP-prone individuals with schizophrenia. Further validation studies in additional populations are required.
AuthorsLior Greenbaum, Robert C Smith, Mordechai Lorberboym, Anna Alkelai, Polina Zozulinsky, Tzuri Lifschytz, Tzuri Lifshytz, Yoav Kohn, Ruth Djaldetti, Bernard Lerer
JournalPsychopharmacology (Psychopharmacology (Berl)) Vol. 220 Issue 3 Pg. 519-28 (Apr 2012) ISSN: 1432-2072 [Electronic] Germany
PMID21947317 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antipsychotic Agents
  • DNA-Binding Proteins
  • Transcription Factors
  • ZFPM2 protein, human
Topics
  • Adult
  • Antipsychotic Agents (adverse effects, therapeutic use)
  • Corpus Striatum (metabolism)
  • Cross-Sectional Studies
  • DNA-Binding Proteins (genetics)
  • Female
  • Genome-Wide Association Study
  • Humans
  • Israel
  • Jews
  • Logistic Models
  • Male
  • Middle Aged
  • Parkinson Disease (physiopathology)
  • Parkinson Disease, Secondary (chemically induced, physiopathology)
  • Polymorphism, Single Nucleotide
  • Schizophrenia (drug therapy)
  • Severity of Illness Index
  • Substantia Nigra (metabolism)
  • Tomography, Emission-Computed, Single-Photon
  • Transcription Factors (genetics)
  • United States

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: