Uncoupling
Protein3 (UCP3)
Association between uncoupling protein 3 gene
and obesity-related phenotypes in the Quebec Family Study
BACKGROUND: UCP3 is a mitochondrial membrane transporter
that is postulated to uncouple oxidative phosphorylation from
ATP synthesis producing heat instead of ATP. Human UCP3 is
mainly expressed in skeletal muscle, which plays an important
role in energy homeostasis and substrate oxidation. Therefore,
UCP3 is a good candidate gene for obesity. MATERIALS AND METHODS:
We analyzed, among 734 subjects from the Quebec Family Study,
a new GA repeat microsatellite located in intervening sequence
(IVS) 6 (GAIVS6) in UCP3 gene, and two already described restriction
fragment length polymorphisms (RFLP) Y210Y(C-->T) and V102I(G-->A).
Covariance analysis across genotypes for different adiposity,
resting energy expenditure, and glucose metabolism variables
was undertaken with age and sex, plus body fat and body mass
for nonadiposity phenotypes, as covariates. RESULTS: We found
strong associations between GAIVS6 and body mass index (p
= 0.0001), fat mass (p = 0.0005), percentage body fat (p =
0.0004), the sum of six skinfold thickness (p = 0.0001), and
leptin level (p = 0.0001). Homozygote for the GAIVS6 240 bp
alleles (15% frequency in QFS) showed higher adiposity than
subjects with the GAIVS6 238 bp allele (70% in QFS). The exons,
the 5' untranslated region= (UTR), and the exon-intron junctions
of UCP3 gene from subjects homozygote for either GAIVS6 238
bp or 240 bp alleles were sequenced in search for mutations.
Variants 5'UTR-55C-->T and Y210Y(C-->T) were detected,
whereas IVS4-36C-->T wasuncovered, but no new exonic or
splice junction mutation was observed. RFLP Y210Y(C-->T)
was not associated to adiposity in QFS; V1021(G-->A) showed
no
variation. CONCLUSION: Our results suggest that some alleles
of UCP3 are involved in the etiology of human obesity. Association
between uncoupling protein 3 gene and obesity-related phenotypes
in the Quebec Family Study. Lanouette CM, Giacobino JP,
Perusse L, Lacaille M, Yvon C, Chagnon M, Kuhne F, Bouchard
C, Muzzin P, Chagnon YC. Association between uncoupling protein
3 gene and obesity-related phenotypes in the Quebec Family
Study. Mol Med 2001 Jul;7(7):433-41
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