Original article 205 Association of catecholamine-O-methyltransferase and 5-HTTLPR genotype with eating disorder-related behavior and attitudes in females with eating disorders Helge Frieling a , Konstanze D. Ro ¨ mer a , Julia Wilhelm a , Thomas Hillemacher a , Johannes Kornhuber a , Martina de Zwaan b , Georg E. Jacoby c and Stefan Bleich a Objective There is growing evidence, that genetic variants contribute to the pathogenesis of anorexia nervosa and bulimia nervosa. Genetic studies have revealed candidate genes, but no satisfactory associations with the disorders have been found so far. The aim of the present study was to evaluate, whether behavioral and attitudinal traits of the disorders can serve as phenotypes with a possible association with two common functional polymorphisms of the monoaminergic pathways. Method Forty-five female in-patients of a specialized hospital for eating disorders were included into the study. Eating disorder symptomatology was assessed using the Eating Disorder Inventory-2. The functional catecholamine-O-methyltransferase (COMT) 158 Val-Met polymorphism and the deletion/insertion polymorphism of the serotonin transporter promoter 5-HTTLPR were determined. Results Carriers of at least one Met-allele of the COMT gene had significantly higher total scores of the Eating Disorder Inventory-2, as well as significantly higher scores on the subscales bulimia, ineffectiveness, interoceptive awareness, maturity fears and impulse regulation. Carriers of the deletion of the 5-HTTLPR had significantly higher scores on the subscales drive for thinness and body dissatisfaction. Conclusion We found associations between the COMT and the 5-HTTLPR polymorphisms and specific clinical, behavioral and attitudinal traits of eating disorders. These polymorphisms may predispose their carriers to exhibit certain symptoms of eating disorders or confer a general risk for more severe forms of these disorders. Psychiatr Genet 16:205–208  c 2006 Lippincott Williams & Wilkins. Psychiatric Genetics 2006, 16:205–208 Keywords: 5-HTTLPR, COMT, eating disorder, Eating Disorder Inventory-2, genotyping, phenotypes a Department of Psychiatry and Psychotherapy, b Department of Psychosomatic Medicine and Psychotherapy, University Erlangen-Nuremberg, Erlangen and c Klinik am Korso, Hospital for Eating Disorders, Bad Oeynhausen, Germany Correspondence and requests for reprints to Dr Helge Frieling, MD, Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University Erlangen-Nuremberg, Schwabachanlage 6, 91054 Erlangen, Germany Tel: + 49 9131 853 4262; fax: + 49 9131 853 4105; e-mail: helge.frieling@psych.imed.uni-erlangen.de Sponsorship: This study was supported by a grant (H.F.) from IZKF (Interdisciplinary Center for Clinical Research), Friedrich-Alexander-University of Erlangen-Nuremberg, Germany. Received 2 June 2006 Accepted 6 June 2006 Introduction There is growing evidence from twin-studies as well as association and linkage analyses, that eating disorders such as anorexia nervosa (AN) and bulimia nervosa (BN) have a genetic basis, contributing to > 50% of the variance in AN (Klump and Gobrogge, 2005). As disturbances of monoaminergic neurotransmission exist in eating disorders, most of the research has targeted serotonin, dopamine and norepinephrine-related genes. Positive findings were reported for two serotonin receptor genes (5HT 2A , 5HT 2C ) and a possible association with AN (reviewed in Bulik and Tozzi, 2004) and for the serotonin transporter gene (5-HTT) for both AN and BN (Di Bella et al., 2000; Fumeron et al., 2001). These findings, however, were not confirmed in replication studies (Hinney et al., 1997; Sundaramurthy et al., 2000; Urwin et al., 2003). Moreover, the findings for functional polymorphisms of the catecholamine- O-methyltransfer- ase (COMT) are inconsistent (Frisch et al., 2001; Gabrovsek et al., 2004; Michaelovsky et al., 2005). In most cases, association studies have not differentiated subtypes or special phenotypes of AN or BN. Recently, a susceptibility locus on chromosome 1 was found for the classic restrictive subtype of AN (Grice et al., 2002). Devlin et al. (2002) selected behavioral traits as covariates into their linkage analysis, which revealed several regions of interest on chromosomes 1, 2 and 13. Siegfried et al. (2004) also reported an association of a polymorphism of the cannabinoid receptor 1 with restrictive AN. 0955-8829  c 2006 Lippincott Williams & Wilkins Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.