Association report 157 II. Serotonin receptor gene polymorphisms and their association with tardive dyskinesia among schizophrenia patients from North India Smita N. Deshpande a , Panchami G. Varma b , Prachi Semwal b , Atmakuri R. Rao c , Triptish Bhatia a , Vishwajit L. Nimgaonkar d , Bernard Lerer e and B.K. Thelma b Psychiatric Genetics 2005, 15:157–158 a Department of Psychiatry, Dr. Ram Manohar Lohia Hospital, New Delhi 110 001, b Department of Genetics, University of Delhi South Campus, Benito Juarez Road, New Delhi 110 021, c Biometrics Division, Indian Agricultural Statistics Research Institute, New Delhi 110 012, India, d Department of Psychiatry, University of Pittsburgh, PA 15213, USA and e Department of Psychiatry, Hadassah-Hebrew University Medical Centre, Ein Karem, Jerusalem 91120, Israel. Sponsorships: This work is supported by Indo-Israel Grants # BT/IC-2/00/Smita/ 99; BT/IC-2/Israel/Deshpande/2002 and the Department of Biotechnology, Government of India, Grant # BT/PR2425/Med/13/089/2001. Correspondence and requests for reprints to B.K. Thelma, Department of Genetics, University of Delhi South Campus, Benito Juarez Road, New Delhi 110 021, India. Tel: + 91 11 24678201; fax: + 91 11 26885270; e-mail: humgen@vsnl.com Tardive dyskinesia (TD) is an adverse irreversible side effect afflicting about 20–30% of all schizophrenia patients receiving typical antipsychotic treatment. An association of two polymorphisms ( – 1438A > G, 102T > C) in 5-hydroxytryptamine receptor 2A(5HTR2A) and an exonic single nucleotide polymorphism (SNP) (Cys23Ser) in HTR2C with TD among the population of Israel and association with only HTR2A in unrelated Chinese Singaporeans have been reported (Segman et al., 2001; Tan et al., 2001), which was not replicated in some other population (Basile et al., 2002). The two most commonly studied polymorphisms in the HTR2A receptor gene, namely 5-HT2A ( – 1438A > G in the promoter) and HTR2A (102T > C, in exon 1) and one polymorphism in the HTR2C receptor gene (68C > G, Cys23Ser in exon 2) (all in Hardy–Weinberg equilibrium in the population) have been investigated in this study. We analyzed a total of 335 patients (mean age 32.42 ± 11.10), of whom 96 (28.66%) were affected with TD. Controls were also recruited from the participating hospitals and the university health center. No significant difference between the distribution of males (N = 182, TD-Y = 59, TD-N = 123) and females (N = 153, TD-Y = 37, TD- N = 116) was observed among the TD-Y and TD-N groups (P = 0.097). In the TD-Y group, males had a higher mean AIMS score than females (males, 6.17 ± 3.67; females, 5.18 ± 3.23; F(1,93) = 4.305, P = 0.041, r 2 = 0.22, power = 0.54). The severity of abnormal involuntary movements was found to increase with age (Pearson’s r = 0.37, P = 0.001). No significant allelic or genotypic association of either the promoter (w 2 = 0.005, df = 1, P = 0.83 and w 2 = 0.9, df = 2, P = 0.64, respectively) or the exonic (w 2 = 0.44, df = 1, P = 0.51 and w 2 = 0.6, df = 2, P = 0.74, respectively) SNPs was observed in the HTR2A gene with TD. For the X-linked gene HTR2C, genotyping results were obtained for 37 TD-Y and 115 TD-N females and 58 TD-Y and 118 TD-N males. The w 2 test revealed no allelic association of this SNP either in females or in males (w 2 = 0.003, df = 1, P = 0.95; w 2 = 0.24, df = 1, P = 0.88, respectively) or genotypic association among either females or males (w 2 = 2.58, df = 2, P = 0.28; w 2 = 0.24, df = 1, P =0.88, respectively). However, in a regression analysis, with TD status as a dependent variable, age was seen to be significantly associated with TD [odds ratio (95% confidence interval) = 1.02(1.00–1.05)]. A possible explanation for the absence of association in our sample set may have been the younger age of the patients. In most of the previous studies where an association was observed with TD, the mean age of the patients was greater than 50 years, while in those where no association was observed, the mean age of the patients was less than 35 years (Segman et al., 2001; Tan et al., 2001). For these differences, Segman and Lerer (2002) suggested that genetically based variations in receptors might become more functionally relevant at an older age when receptor reserve is reduced for reasons related to the aging process. Drug-induced changes in receptors in the striatum and aging-related degenerative effects have also been speculated to affect the development of TD (Jeste and Caligiuri, 1993). Though the present study was conducted on a reasonably large sample size, we failed to observe any association. As complex traits are known to be governed by several genes of minor effect with their contributions varying between different ethnic groups, additional studies evaluating SNPs in other candidate genes and analyzing gene interactions are warranted. 0955-8829  c 2005 Lippincott Williams & Wilkins Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.