5-HT2A RECEPTOR POLYMORPHISM AND SUSCEPTIBILITY TO TARDIVE DYSKINESIA IN PATIENTS WITH CHRONIC SCHIZOPHRENIARonnen H. Segman, Uriel Heresco Levy, Boris Finkel, David Greenberg, Avi Yakir, Michael Shlaffman, Abe Dorevich, Tanya Goltser, Bernard Lerer*.Biological Psychiatry Laboratory, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. Email: sronnen@md2.huji.ac.il or lerer@cc.huji.ac.il Three polymorphisms in the 5-HT2A receptor gene, one intronic (T102C), one in the coding region (His452Tyr) and one in the promoter (-1438A/G), were examined for association with tardive dyskinesia (TD). The sample included 57 chronic schizophrenia patients with TD who were matched to 63 schizophrenia patients without TD. For the T102C polymorphism, there was a significant excess of the 2 (C) allele in the patients with TD (60.5% vs. 46.8%; x2=4.5, p=.03; OR 1.7 95%CI 1.1-2.9) and of 22 (CC) versus other genotypes (40.4% vs. 15.9%; x2=9.1, p=.003; OR 3.6 95%CI 1.5-7.9). Similar results were obtained for the A-1438G promoter polymorphism, which was in linkage disequilibrium with T102C. There was an excess of G-1438 allele in patients with TD, 59.4% vs. 43.6%; x2=6.1, p=.01; OR 1.9 95%CI 1.1-3.2) and of GG genotypes (37.9% vs. 19.4%; x2=5.1, p=.02; OR 2.6 95%CI 1.1-5.6). Patients carrying the T102C, CC genotype and the A-1438G, GG genotype had significantly higher AIMS distal dyskinesia scores and more incapacitation than patients with other genotypes. In contradistinction, the His452Tyr polymorphism showed no association at all with TD. Previously reported association of the T102C and -1438A/G polymorphisms in the 5-HT2A receptor gene with schizophrenia, may reflect association of a sub-group of patients with susceptibility to abnormal involuntary movements related to antipsychotic drug exposure. (Supported in part by the Hadassit Applied Research Fund and the Israel India Genome Research Project).
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