Variations in the uncoupling protein-3 gene are associated with specific obesity phenotypes.
OBJECTIVE
Uncoupling protein 3 (UCP-3) uncouples oxidative metabolism from ATP synthesis, resulting in the production of heat instead of energy storage. Single nucleotide polymorphisms (SNPs) in UCP-3 might result in a reduced function or expression of UCP-3 and therefore lead to an increased capacity to store energy as fat.


METHODS
We conducted a population-based, cross-sectional single-center study among 400 Dutch men between 40 and 80 years.


METHODS
Seven SNPs in the UCP-3 gene were genotyped by means of an allele-specific real-time TaqMan PCR. Linear regression analyses were performed to examine the independent effects of these SNPs on obesity phenotypes.


RESULTS
We found a significant association between homozygosity for the minor allele of rs647126, rs1685356, and rs2075577 and an increase in body mass index (BMI; P=0.033, P=0.016, and P=0.019 respectively). Heterozygosity for rs1685354 was associated with a significant decrease in visceral fat mass (P=0.030).


CONCLUSIONS
Our results suggest that genetic variations in the UCP-3 gene are associated with an increase in BMI. A plausible mechanism by which these SNPs lead to an increase in BMI is that due to these SNPs, the UCP-3 activity might be decreased. As a result, uncoupling activity may also decrease, which will lead to an increase in body weight and BMI.
van Abeelen
Annet F M
AF
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Room STR 6.131, PO Box 85500, 3508 GA Utrecht, The Netherlands.
de Krom
Mariken
M
Hendriks
Judith
J
Grobbee
Diederick E
DE
Adan
Roger A H
RA
van der Schouw
Yvonne T
YT
D000255:Adenosine Triphosphate / Q000378:metabolism; D000273:Adipose Tissue / Q000502:physiology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007473:Ion Channels / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism; D009426:Netherlands / Q000453:epidemiology; D009765:Obesity / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D000071247:Uncoupling Protein 3
D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604392:UCP3 protein, human; D000071247:Uncoupling Protein 3; D000255:Adenosine Triphosphate