Uncoupling Protein-2 45-Base Pair Insertion/Deletion Polymorphism: Is There an Association with Severe Obesity and Weight Loss in Morbidly Obese Subjects?

Background: Uncoupling proteins are attractive candidate genes for obesity and type 2 diabetes mellitus. Our aim was to investigate the potential association of the uncoupling protein-2 (UCP2) 45-bp insertion/deletion (ins/del) polymorphism with obesity, as well as the potential effect of this polymorphism on weight loss variability in severely obese subjects. Methods: A total of 158 severely obese subjects (94 without and 64 with metabolic syndrome) and 91 age and sex-matched lean controls were recruited. A subgroup of 124 obese patients participated in a 3-month weight loss program. Anthropometric and metabolic variables were measured. Participants were genotyped for the UCP2 ins/del polymorphism. Results: Allelic frequency differed neither between obese subjects and controls (P = 0.56), nor between obese subjects with versus without metabolic syndrome (P = 0.58). At 3 months, metabolically healthy subjects carrying the insertion allele had significantly greater reduction in body mass index (P = 0.029) and fat-free mass (P = 0.013) and a borderline significant improvement in the homeostatic model assessment index (P = 0.048). Conclusion: There is no association of the UCP2 ins/del polymorphism with morbid obesity in our population, but this genotype appears to be linked with a favorable response to dietary changes in metabolically healthy obese subjects.