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The Association Study of Polymorphisms in DAT, DRD2, and COMT Genes and Acute Extrapyramidal Adverse Effects in Male Schizophrenic Patients Treated With Haloperidol

Živković, Maja; Mihaljević-Peleš, Alma; Božina, Nada; Šagud, Marina; Nikolac Perković, Matea; Vuksan-Cusa, Bjanka; Muck-Šeler, Dorotea (2013) The Association Study of Polymorphisms in DAT, DRD2, and COMT Genes and Acute Extrapyramidal Adverse Effects in Male Schizophrenic Patients Treated With Haloperidol. Journal of clinical psychopharmacology, 33 (5). pp. 593-599. ISSN 0271-0749

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Extrapyramidal symptoms (EPSs) are common adverse effects of antipsychotics. The development of acute EPSs could depend on the activity of dopaminergic system and its gene variants. The aim of this study was to determine the association between dopaminergic type 2 receptor (DRD2) dopamine transporter (SLC6A3) and catechol-O-methyltransferase (COMT) gene polymorphisms and acute EPSs in 240 male schizophrenic patients treated with haloperidol (15-mg/d) over a period of 2 weeks. Acute EPSs were assessed with Simpson-Angus Scale. Three dopaminergic gene polymorphisms, the DRD2 Taq1A, the SLC6A3 VNTR, and the COMT Val158Met, were determined. Extrapyramidal symptoms occurred in 116 (48.3%) of patients. Statistically significant associations were found for SLC6A3 VNTR and COMT Val158Met polymorphisms and EPS susceptibility. Patients with SLC6A3 9/10 genotype had almost twice the odds to develop EPSs compared with those with all other SLC6A3 genotypes (odds ratio, 1.9 ; 95% confidence interval, 1.13Y3.30), and patients with COMT Val/Met genotype had 1.7 times greater odds to develop EPSs than those with all other COMT genotypes (odds ratio, 1.7 ; 95% confidence interval, 1.01-2.88). There was no statistically significant association between genotype and allele frequencies of DRD2, SLC6A3, or COMT polymorphisms and the development of particular EPSs. In conclusion, the results of the present study showed for the first time the association between acute haloperidol-induced EPSs and SLC6A3 VNTR and COMT Val158Met polymorphisms. Although the precise biological mechanisms underlying these findings are not yet understood, the results suggest that the dopaminergic gene variations could predict the vulnerability to the development of the acute EPSs in haloperidol-treated schizophrenic patients.

Item Type: Article
Uncontrolled Keywords: schizophrenia; haloperidol; acute extrapyramidal adverse effects; DRD2; SLC6A3; COMT
Subjects: BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences
Divisions: Division of Molecular Medicine
Project titleProject leaderProject codeProject type
Pharmacogenomics and proteomics of serotonergic and catecholaminergic system (Farmakogenomika i proteomika serotoninskog i kateholaminskog sustava)-Dorotea Muck-Šeler098-0982522-2457MZOS
Molecular basis and treatment of psychiatric and stress related disorders (Molekularna podloga i liječenje psihijatrijskih i stresom izazvanih poremećaja)-Nela Pivac098-0982522-2455MZOS
Pharmacogenetic varability of psychiatric patients (Farmakogenetska varijabilnost u psihijatrijskih bolesnika)-Alma Mihaljević-Peleš108-1083509-3513MZOS
Depositing User: Matea Nikolac Perković
Date Deposited: 02 Dec 2015 16:58
DOI: 10.1097/JCP.0b013e31829abec9

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