Impact of the v/v 55 polymorphism of the uncoupling protein 2 gene on 24-h energy expenditure and substrate oxidation.
OBJECTIVE
The gene that codes for a novel uncoupling protein, UCP2, has been 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 expenditure 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 fragment length polymorphism-generating polymerase chain reaction.


RESULTS
Age, gender and body fat were not different between groups, the number of subjects in each groups was A/A: 35% (n=21), A/V: 48% (n=29), and 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 than in the A/A and A/V genotypes. The V/V had approximately 20% higher 24-h spontaneous 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 composition. 24-h RQ adjusted for energy balance, age, sex and spontaneous physical 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 enhanced metabolic efficiency and lower fat oxidation than the A/A and A/V genotypes.
Astrup
A
A
Research Department of Human Nutrition, The Royal Veterinary and Agricultural University, Frederiksberg, Denmark. ast@kvl.dk
Toubro
S
S
Dalgaard
L T
LT
Urhammer
S A
SA
Sorensen
T I
TI
Pedersen
O
O
D000328:Adult; D000409:Alanine; D001823:Body Composition; D001824:Body Constitution; D003062:Codon; D004734:Energy Metabolism / Q000235:genetics*; D015444:Exercise; D005260:Female; D005838:Genotype; D006801:Humans; D007473:Ion Channels; D008297:Male; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D012150:Polymorphism, Restriction Fragment Length; D011506:Proteins / Q000737:chemistry / Q000235:genetics*; D014475:Uncoupling Agents / Q000737:chemistry; D000071246:Uncoupling Protein 2; D014633:Valine
D003062:Codon; D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; C000604389:UCP2 protein, human; D014475:Uncoupling Agents; D000071246:Uncoupling Protein 2; D014633:Valine; D000409:Alanine