Mutational analysis of the UCP2 core promoter and relationships of variants with obesity.
OBJECTIVE
To identify polymorphisms in the human uncoupling protein 2 gene (UCP2) promoter and to investigate whether these were associated with obesity or weight gain.


METHODS
The human UCP2 promoter was characterized by reporter gene analysis in cell lines derived from skeletal muscle, white adipose tissue, and embryonic tissue. We analyzed the core promoter for polymorphisms in 60 obese subjects. A prevalent polymorphism, the -866 G/A variant, was investigated for association with obesity in 749 men obese as young adults and 816 men of the same age representing the background population. Genotype-phenotype interaction studies were performed in two other population-based samples: one group of middle-aged-to-elderly Danish subjects (mean age, 53 years; range, 30 to 88 years) and one group of 60-year-old Danish subjects.


RESULTS
The region up to -1202 bp relative to the UCP2 transcription initiation site gave rise to the highest promoter activity. Eight mutations in this region were identified comprising -866 G/A, -850 G/A, -337 G/C, -41 G/T, -28 insertion T, -5 insertion (cactgcgaagccc), +45 C/T, and +53 G/C, but none of these was associated with consistent alterations in BMI, body fat content, weight gain, or fasting levels of plasma glucose and serum insulin.


CONCLUSIONS
Variation of the UCP2 promoter including the single common variant (-866 A/G) is not associated with obesity or obesity-related intermediary phenotypes in Danish subjects.
Dalgaard
Louise T
LT
Steno Diabetes Center and Statens Serum Institute, 5 Artillerivej, Gentofte, DK 2300 Copenhagen, Denmark. ltd@ssi.dk
Andersen
Gitte
G
Larsen
Lesli H
LH
Sørensen
Thorkild I A
TI
Andersen
Teis
T
Drivsholm
Thomas
T
Borch-Johnsen
Knut
K
Fleckner
Jan
J
Hansen
Torben
T
Din
Nanni
N
Pedersen
Oluf
O
D000273:Adipose Tissue; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002460:Cell Line; D004252:DNA Mutational Analysis; D003718:Denmark; D004622:Embryo, Mammalian; D005260:Female; D017930:Genes, Reporter / Q000235:genetics; D005838:Genotype; D006801:Humans; D007473:Ion Channels; D007668:Kidney; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D051379:Mice; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics*; D018482:Muscle, Skeletal; D009154:Mutation; D009765:Obesity / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D000071246:Uncoupling Protein 2
D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; C000604389:UCP2 protein, human; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2