Impact of the v/v 55 polymorphism of the uncoupling protein 2 gene on 24-henergy expenditure and substrate oxidation

OBJECTIVE: The gene that codes for a novel uncoupling protein, UCP2, has be en linked to obesity in animal models. Markers encompassing the UCP2 locus have been linked to energy expenditure in humans. We studied the role of a common amino acid substitution, replacing an alanine (A) with a valine (V) at codon 55, of the coding region of the UCP2 gene for 24-h energy expendit ure and respiratory quotient (RQ) in healthy subjects. METHODS: 24-h energy expenditure and RQ were measured in calorimeters in 60 healthy subjects. The UCP2 polymorphism was determined by restriction frag ment length polymorphism-generating polymerase chain reaction. RESULTS: Age, gender and body fat were not different between groups, the nu mber of subjects in each groups was A/A: 35% (n = 21), A/V: 48% (n = 29), a nd V/V: 17% (n = 10). Twenty-four-hour energy expenditure, adjusted for fat -free mass, fat mass, and spontaneous physical activity, was 311 kJ/d lower (95% confidence interval: 24-598 kJ/d, P = 0.03) in the V/V homozygotes th an in the A/A and A/V genotypes. The V/V had similar to 20% higher 24-h spo ntaneous physical activity, particularly higher at night (P<0.005). Energy expenditure due to higher spontaneous physical activity counteracted the V/ V group's lower 24-h resting energy expenditure for a given body size and c omposition. 24-h RO adjusted for energy balance, age, sex and spontaneous p hysical activity, was higher in the V/V homozygotes than in the AA and A/V groups (P<0.05). CONCLUSIONS: Subjects with the V/V genotype of the UCP2 gene exhibit an enh anced metabolic efficiency and lower fat oxidation than the A/A and A/V gen otypes.