Variants in the DRD2 locus and antipsychotic-related prolactin levels: A meta-analysis

PSYCHONEUROENDOCRINOLOGY

卷:72

Article

Miura, Itaru^1,2  Zhang, Jian-Ping^1,3,4  Hagi, Katsuhiko^1,5  Lencz, Todd^1,3,4,6  Kane, John M.^1,3,4,6  Yabe, Hirooki²  Malhotra, Anil K.^1,3,4,6  Correll, Christoph U.^1,3,4,6 

[1] North Shore Long Isl Jewish Hlth Syst, Zucker Hillside Hosp, Psychiat Res, Glen Oaks, NY USA

[2] Fukushima Med Univ, Sch Med, Dept Neuropsychiat, Fukushima, Japan

[3] Hofstra North Shore LIJ Sch Med, Hempstead, NY USA

[4] Feinstein Inst Med Res, Manhasset, NY USA

[5] Sumitomo Dainippon Pharma Co Ltd, Med Affairs, Tokyo, Japan

[6] Albert Einstein Coll Med, Bronx, NY 10467 USA

关键词: Antipsychotics;    Prolactin;    Hyperprolactinemia;    Schizophrenia;    DRD2;    Meta-analysis;   

DOI  :  10.1016/j.psyneuen.2016.06.002

来源: Elsevier

【 摘 要 】

Background: 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. Methods: Systematic literature search (5/8/2015) was performed to find published studies of pharmacogenetic associations between two DRD2 variants, Taq1A (rs1800497) and -141CIns/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). Results: 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 Taq1AA1 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%). Discussion: 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. (C) 2016 Elsevier Ltd. All rights reserved.

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