title: Variants in the DRD2 locus and antipsychotic-related prolactin levels: A meta-analysis.
abstract: Although dopamine D2 receptor antagonists lead to dose-dependent prolactin (PRL) elevations proportionate to their D2 affinity, considerable inter-individual differences exist. We conducted a meta-analytic review of associations between genetic variations in the dopamine D2 receptor gene (DRD2) and PRL levels in antipsychotic-treated subjects.
  
  
  
  Systematic literature search (5/8/2015) was performed to find published studies of pharmacogenetic associations between two DRD2 variants, Taq1A (rs1800497) and -141C Ins/Del (rs1799732), and PRL levels during antipsychotic treatment (excluding aripiprazole). Patients were included independent of age or diagnosis. Random effects models were used and Hedges' g was calculated as the effect size measure. Subgroup analyses explored the effect of sex and diagnosis, (males vs females; schizophrenia vs non-schizophrenia).
  
  
  
  Altogether, 11 studies (n=1034, schizophrenia-spectrum=475) for Taq1A polymorphism, and 4 studies (n=451, schizophrenia-spectrum=274) for -141C Ins/Del polymorphism, each reporting on PRL levels but not on the proportion of patients with hyperprolactinemia, were meta-analyzed. Across all patients, there was no statistically significant association between PRL levels and either DRD2 Taq1A genotype or DRD2 -141C Ins/Del genotype. However, in patients with schizophrenia, PRL levels were significantly higher in DRD2 Taq1A A1 carriers than A1 non-carriers (studies=5, n=475, Hedges' g=0.250, 95% CI=0.068-0.433, p=0.007, I(2)=0%).
  
  
  
  Although there was no significant association between either DRD2 Taq1A genotype or DRD2 -141C Ins/Del genotype and PRL levels in all included patients, our results suggest that DRD2 Taq1A genotype may affect antipsychotic-related PRL levels in patients with schizophrenia. Because of the small sample size, further studies are needed to confirm these results.
authors.affiliation: The Zucker Hillside Hospital, Psychiatry Research, North Shore-Long Island Jewish Health System, Glen Oaks, NY, USA; Department of Neuropsychiatry, Fukushima Medical University School of Medicine, Fukushima, Japan.
authors.forename: Itaru
authors.initials: I
authors.lastname: Miura
authors.affiliation: The Zucker Hillside Hospital, Psychiatry Research, North Shore-Long Island Jewish Health System, Glen Oaks, NY, USA; Hofstra North Shore LIJ School of Medicine, Hempstead, NY, USA; The Feinstein Institute for Medical Research, Manhasset, NY, USA.
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Zhang
authors.affiliation: The Zucker Hillside Hospital, Psychiatry Research, North Shore-Long Island Jewish Health System, Glen Oaks, NY, USA; Sumitomo Dainippon Pharma Co., Ltd., Medical Affairs, Tokyo, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Hagi
authors.affiliation: The Zucker Hillside Hospital, Psychiatry Research, North Shore-Long Island Jewish Health System, Glen Oaks, NY, USA; Hofstra North Shore LIJ School of Medicine, Hempstead, NY, USA; The Feinstein Institute for Medical Research, Manhasset, NY, USA; Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Todd
authors.initials: T
authors.lastname: Lencz
authors.affiliation: The Zucker Hillside Hospital, Psychiatry Research, North Shore-Long Island Jewish Health System, Glen Oaks, NY, USA; Hofstra North Shore LIJ School of Medicine, Hempstead, NY, USA; The Feinstein Institute for Medical Research, Manhasset, NY, USA; Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Kane
authors.affiliation: Department of Neuropsychiatry, Fukushima Medical University School of Medicine, Fukushima, Japan.
authors.forename: Hirooki
authors.initials: H
authors.lastname: Yabe
authors.affiliation: The Zucker Hillside Hospital, Psychiatry Research, North Shore-Long Island Jewish Health System, Glen Oaks, NY, USA; Hofstra North Shore LIJ School of Medicine, Hempstead, NY, USA; The Feinstein Institute for Medical Research, Manhasset, NY, USA; Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Malhotra
authors.affiliation: The Zucker Hillside Hospital, Psychiatry Research, North Shore-Long Island Jewish Health System, Glen Oaks, NY, USA; Hofstra North Shore LIJ School of Medicine, Hempstead, NY, USA; The Feinstein Institute for Medical Research, Manhasset, NY, USA; Albert Einstein College of Medicine, Bronx, NY, USA. Electronic address: ccorrell@lij.edu.
authors.forename: Christoph U
authors.initials: CU
authors.lastname: Correll
mesh_terms: D014150:Antipsychotic Agents / Q000494:pharmacology*; D006801:Humans; D011388:Prolactin / Q000187:drug effects*; D011618:Psychotic Disorders / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism
chemical_list: D014150:Antipsychotic Agents; C581293:DRD2 protein, human; D017448:Receptors, Dopamine D2; D011388:Prolactin
keywords: Antipsychotics; DRD2; Hyperprolactinemia; Meta-analysis; Prolactin; Schizophrenia