OBJECTIVE: Given the important role of the beta2-adrenoceptor (beta2-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) beta2-AR polymorphism in the susceptibility to obesity and its metabolic complications 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), systolic 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. Beta2-AR Gln27Glu genotypes were determined by restriction fragment length polymorphism (RFLP)-polymerase chain reaction (PCR). RESULTS: Glu27 homozygous obese men had significantly 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 beta2-adrenoceptor may be a risk factor in men but not in women for the accumulation of visceral fat and for its association with the development of type 2 diabetes mellitus.