Association between the T102C polymorphism of the serotonin-2A receptor gene and schizophrenia ☆ Concepcion Vaquero Lorenzo a,1 , Enrique Baca-Garcia b, ⁎ , Montserrat Diaz-Hernandez a,1 , Carlota Botillo-Martin b , M. Mercedes Perez-Rodriguez c,2 , Carolina Fernandez-Ramos a,1 , M. Dolores Saiz-Gonzalez c,2 , Francisco J. Quintero-Gutierrez b , Jeronimo Saiz-Ruiz c,2 , Jose Fernandez Piqueras a,1 , Jose Luis Gonzalez de Rivera b , Jose de Leon d,3 a Department of Genetics, Autonoma University of Madrid, Edificio de Biología, Facultad de Ciencias, Calle Darwin, 2. 28049, Cantoblanco (Madrid), Spain b Department of Psychiatry, Fundacion Jimenez Diaz University Hospital, Avenida Reyes Católicos 2. 28040, Madrid, Spain c Department of Psychiatry, Ramón y Cajal University Hospital, Carretera de Colmenar Viejo Km 9,100 Madrid 28034, Spain d Mental Health Research Center (UK MHRC) at Eastern State Hospital, 627 West Fourth St., Lexington, KY 40508, USA Received 10 February 2006; received in revised form 24 March 2006; accepted 30 April 2006 Available online 8 June 2006 Abstract Studies have shown an association between the T102C polymorphism of the 5HT2a receptor gene and schizophrenia. However, negative findings have also been reported. We conducted a case-control study of the T102C polymorphism in Spanish Caucasians. We compared T102C polymorphism genotypes and allele frequencies in 188 schizophrenia patients and 440 healthy controls. There were significant differences in the distribution of the three genotypes (TT, TC and CC) and in the allele frequencies in controls and schizophrenics. The C allele was more frequent in schizophrenia patients than in healthy controls. The Cochrane-Armitage test for trend indicated a significant dosage effect for schizophrenia of the risk allele (C). © 2006 Elsevier Inc. All rights reserved. Keywords: Schizophrenia; Serotonin 5-HT2A receptor; T102C polymorphism 1. Introduction Schizophrenia is a major psychiatric illness affecting approx- imately 1% of the world population. Research findings have supported the hypothesis that schizophrenia is an inherited disorder (Kendler and Diehl, 1993; McGuffin et al., 1995). The serotonin (5HT) system has been implicated in the pathogenesis of schizophrenia (Roth and Meltzer, 1995). 5HT2 receptors have received much attention due to their role in the therapeutic actions of clozapine (Abdolmaleky et al., 2004). In the T102C polymorphism of the 5HT2a receptor gene, the base in nucleotide position 102 may be thymine (T) or cytosine (C), with three possible genotypes TT, TC or CC. This mutation does not result in any change in the amino-acid sequence of the 5HT2a receptor, as both alleles encode for a serine in codon 34 (Warren et al., 1993). The aim of this study is to test the association between the T102C polymorphism and schizophrenia in Spanish Caucasians. 2. Methods 2.1. Sample Schizophrenia patients (N = 188, 94 women and 94 men) and healthy blood donors without personal or family history of Progress in Neuro-Psychopharmacology & Biological Psychiatry 30 (2006) 1136 – 1138 www.elsevier.com/locate/pnpbp Abbreviations: df, degrees of freedom; OR, odds ratio; PCR, polymerase chain reaction; 5HT, serotonin ☆ The work was performed at the Department of Psychiatry, Ramón y Cajal University Hospital, Madrid, Spain. ⁎ Corresponding author. Servicio de Psiquiatría, Fundación Jiménez Díaz, Avenida Reyes Católicos 2, 28040 Madrid, Spain. Tel./fax: +34 91 550 49 87. E-mail addresses: ebacgar2@yahoo.es (E. Baca-Garcia), merperez@yahoo.com (M.M. Perez-Rodriguez). 1 Tel.: +34 914978339. 2 Tel.: +34 91 336 83 93. 3 Tel.: +1 859 246 7487; fax: +1 859 246 7019. 0278-5846/$ - see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.pnpbp.2006.04.027