Clinical Endocrinology (2003) 59, 476–481 476 © 2003 Blackwell Publishing Ltd Blackwell Publishing Ltd. The glutamine 27 glutamic acid polymorphism of the β 2 - adrenoceptor gene is associated with abdominal obesity and greater risk of impaired glucose tolerance in men but not in women: a population-based study in Spain J. L. González Sánchez*, A. M. Proenza†, M. T. Martínez Larrad*, J. M. Ramis†, C. Fernández Pérez*, A. Palou† and M. Serrano Ríos* * Departamento de Medicina Interna II, Hospital Universitario Clínico San Carlos, Madrid and † Departament de Biologia Fonamental i Ciències de la Salut, Universitat de les Illes Balears, Palma de Mallorca, Spain (Received 13 January 2003; returned for revision 9 April 2003; finally revised 10 April 2003; accepted 20 May 2003) Summary OBJETIVE Given the important role of the β 2 -adrenoceptor (β 2 -AR) in lipid mobilization and the lack of studies in Southern European countries, the aim of this study was to investigate the role of the glutamine 27 glutamic acid (Gln27Glu) β 2 -AR polymorphism in the susceptibility to obesity and its metabolic complica- tions in a population-based nationwide multicentre study in Spain, especially focusing on the hypothetical influence of gender. DESIGN Cross-sectional population-based study. PATIENTS We studied 666 nonrelated adults (47·9% men and 52·1% women), aged 35–64 years, chosen randomly from a nationwide population-based survey of obesity, and related conditions including insulin resistance and cardiovascular risk factors. MEASUREMENTS Body mass index (BMI), waist-to-hip ratio (WHR), sagittal abdominal diameter (SAD), systo- lic and diastolic blood pressure, fasting and 2-h post- glucose load glycaemic levels, total cholesterol, high density lipoprotein (HDL)- and low density lipoprotein (LDL)-cholesterol, triglycerides, insulin, proinsulin and leptin plasma levels were measured. β 2 -AR Gln27Glu genotypes were determined by restriction fragment length polymorphism (RFLP)-polymerase chain reac- tion (PCR). RESULTS Glu27 homozygous obese men had signi- ficantly higher BMI and SAD mean values than both heterozygous and Gln27 homozygous obese men. Two-hour post-load plasma glucose concentration was higher in Glu27 homozygous than in Gln27 homozygous in the whole population and only in men when stratified by gender. No differences according to the genotype were found for the rest of the parameters studied, including homeostasis model assessment (HOMA), insulin, proinsulin and leptin levels, but for total and LDL-cholesterol these increased in men. We did not find differences in the anthropometrical and biochemical parameters according to the genotype in women. Multivariate logistic regression analysis showed that Glu27 homozygosity after adjustment for SAD was associated with type 2 diabetes mellitus. CONCLUSIONS Our results suggest that the glutamic acid 27 allele of the β 2 -adrenoceptor may be a risk factor in men but not in women for the accumulation of visceral fat and for its association with the develop- ment of type 2 diabetes mellitus. Obesity is a complex syndrome reflecting an imbalance between energy intake and expenditure and it is a well-known risk factor for dyslipidaemias, type 2 diabetes mellitus, cardiovascular disease and other related metabolic diseases (Pi-Sunyer, 1993; Palou et al ., 2000; Proenza et al ., 2000). Obesity in humans is under strong genetic influence as a result of the interaction between a number of partially identified genes and lifestyle-related environmental factors. Among the many candidate genes, the β adrenergic receptor ( β -AR) genes are of special interest given their role in lipid mobilization, as lipolysis is stimulated by catecholamines through β -ARs, and inhibited through α -ARs, and the β 2 -AR is the main lipolytic receptor in white human adipose tissue (Arner & Hoffstedt, 1999). Several polymorphisms in the coding region of the β 2 -AR gene have been reported to alter several receptor functions (Green et al., 1994; Liggett, 1997); in particular, the glutamine 27 glutamic acid (Gln27Glu) polymorphism has been suggested as a likely candidate to have an impact on human obesity (Large et al ., 1997). However, with regard to the association Correspondence: Professor Manuel Serrano Ríos, Cea Bermúdez 66, 5° G. 28003 Madrid, Spain. Tel.: + 34 91 3303385/87; Fax: + 34 91 4429705; E-mail: uinvest7@hcsc.insalud.es