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Variations in the uncoupling protein-3 gene are associated with specific obesity phenotypes
Annet F M van Abeelen1, Mariken de Krom, Judith Hendriks
1Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Room STR 6.131, PO Box 85500, 3508 GA Utrecht, The Netherlands.
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.
Design:
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.
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