Appetite 50 (2008) 260–265 Research report Impact of the -1438G4A polymorphism in the serotonin 2A receptor gene on anthropometric profile and obesity risk: A case–control study in a Spanish Mediterranean population Jose´ V. Sorlı´ a,b,c , Francesc France´s a,c , Jose´ I. Gonza´lez a,c , Marisa Guille´n a , Olga Portole´s d , Antonio Sabater a,c , Oscar Coltell d , Dolores Corella a,c,Ã a Genetic and Molecular Epidemiology Unit, Department of Preventive Medicine and Public Health, Valencia University, Valencia, Spain b Centro de Salud de Atencio´n Primaria de Xirivella, Valencia, Spain c CIBER Fisiopatologı´a de la Obesidad y Nutricio´n, Instituto de Salud Carlos III, Madrid, Spain d Departamento de Lenguajes y Sistemas Informa´ticos, Universitat Jaume I, Castello´n, Spain Received 6 May 2007; received in revised form 1 July 2007; accepted 25 July 2007 Abstract Research into the genetic factors that regulate food intake is arousing great interest. The polymorphism -1438G4A in the serotonin 2A receptor or 5-hydroxytriptamine (5-HT) type 2A receptor (5-HTR2A) gene has been associated with alterations in food intake such as anorexia and bulimia. However, its association with obesity has not been studied to the same extent. Our aim, therefore, was to estimate the association between the -1438G4A polymorphism and obesity risk and related anthropometric variables in a Spanish Mediterranean population. A case–control study including 303 cases and 606 controls paired by gender and age was undertaken. The association between the -1438G4A polymorphism and obesity and other anthropometric measures was studied. No association with obesity risk was observed. However, when only the obese group was analyzed, it was observed that AA subjects presented a lower body mass index (BMI) than G allele carriers (35.275.3 kg/m 2 vs 37.577.8 kg/m 2 ; P ¼ 0.039). Moreover, significant differences were also obtained in waist perimeter that was lower in AA subjects compared to G allele carriers (105711 cm vs 112717 cm; P ¼ 0.011). In conclusion, although the -1438G4A polymorphism is not a relevant marker for obesity risk, this variant may play a role in determining BMI in obese subjects. r 2007 Elsevier Ltd. All rights reserved. Keywords: Obesity; Serotonin; Genetics; Control of food intake; Body mass index; Waist; Genetics Introduction Research into the factors that regulate food intake is arousing great interest in obtaining better knowledge on its practical application in the prevention and control of obesity (Alonso-Alonso & Pascual-Leone, 2007; Keller, Pietrobelli, Must, & Faith, 2002; Rolls, 2007). Among the genetic factors involved (Rankinen et al., 2006), the gene codifying the serotonin 2A receptor or 5-hydroxytripta- mine (5-HT) type 2A receptor (5-HTR2A) has been one of the most studied. 5-HT is an amine synthesized in the neurons that acts as a neurotransmitter, modulating the physiological mechanisms of feeding through its interac- tion with the postsynaptic receptor 5-HTR2A (Simansky, 1996). The 5-HTR2A gene is located in 13q14-21 and contains three exons separated by two introns (Chen, Yang, Grimsby, & Shih, 1992). Several polymorphic variants have been described in this gene; among them: - 1438G4A, T25N, T102C, I197V, A447V and H452Y (Enoch et al., 1998; Harvey et al., 2003; Inayama et al., 1996). All of these variants have been analyzed within the framework of genetic determinants of various psychotic disturbances (Arranz et al., 1998; Enoch et al., 1998; Harvey et al., 2003; Inayama et al., 1996), with the polymorphism -1438G4A (rs6311), in the regulatory region, being specifically associated with alterations in ARTICLE IN PRESS www.elsevier.com/locate/appet 0195-6663/$ - see front matter r 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.appet.2007.07.011 Ã Corresponding author. Department of Preventive Medicine, School of Medicine, Avda, Blasco Iban˜ez, 15, 46010 Valencia, Spain. E-mail address: dolores.corella@uv.es (D. Corella).