Variations in the uncoupling protein-3 gene are associated with specific obesity phenotypes.

Abstract

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.

• Authors: Annet F M van Abeelen, Mariken de Krom, Judith Hendriks, Diederick E Grobbee, Roger A H Adan, Yvonne T van der Schouw
• Journal: European journal of endocrinology (Eur J Endocrinol) Vol. 158 Issue 5 Pg. 669-76 (May 2008) ISSN: 1479-683X [Electronic] England
• PMID: 18426825 (Publication Type: Journal Article)

Chemical References

• Ion Channels
• Mitochondrial Proteins
• UCP3 protein, human
• Uncoupling Protein 3
• Adenosine Triphosphate

Topics

• Adenosine Triphosphate (metabolism)
• Adipose Tissue (physiology)
• Adult
• Aged
• Aged, 80 and over
• Body Mass Index
• Cross-Sectional Studies
• Genetic Predisposition to Disease (epidemiology)
• Genetic Variation
• Genotype
• Humans
• Ion Channels (genetics, metabolism)
• Male
• Middle Aged
• Mitochondrial Proteins (genetics, metabolism)
• Netherlands (epidemiology)
• Obesity (genetics, metabolism, physiopathology)
• Phenotype
• Polymorphism, Single Nucleotide
• Uncoupling Protein 3