Evidence that single nucleotide polymorphism in the uncoupling protein 3 (UCP3) gene influences fat distribution in women of European and Asian origin.
OBJECTIVE
Uncoupling proteins are mitochondrial transmembrane carriers implicated in the regulation of energy balance. Dysfunction of UCP3 (the predominant uncoupling protein in skeletal muscle) might therefore be expected to reduce thermogenic capacity, alter energy homeostasis and influence predisposition to obesity and Type II (non-insulin-dependent) diabetes mellitus. A variant in the putative promoter region of UCP3 (-55 c-->t) has recently been identified, and an association with obesity reported in French subjects. Our aim was to study the pathophysiological role of this variant in diabetes-related and obesity-related traits using two distinct ethnic populations.


METHODS
The -55 c-->t variant was genotyped in 85 South Indian and 150 European parent-offspring trios ascertained through Type II diabetic probands and in 455 South Indian subjects initially recruited to an urban survey into the prevalence of diabetes.


RESULTS
In South Indian and European parent-offspring trios there was no preferential transmission of either allele at the -55 c-->t polymorphism to diabetic offspring (South Indians, p = 0.60; Europeans, p = 0.15). When family members were analysed for intermediate traits, the t-allele was associated with increased waist-to-hip ratio but only in females (South Indian mothers p = 0.036, daughters p = 0.032: European mothers p = 0.037, daughters p = 0.14). These findings were replicated in South Indian females from the population-based survey (p = 0.039).


CONCLUSIONS
The consistent association between the t-allele at this locus and increased waist-to-hip ratio in women from three separate data sets indicates that variation at this polymorphism (or another locus with which it is in linkage disequilibrium) influences fat distribution but that this effect is restricted to females.
Cassell
P G
PG
Department of Diabetes and Metabolic Medicine, St Bartholomews and Royal London School of Medicine and Dentistry, Queen Mary and Westfield College, London, UK.
Saker
P J
PJ
Huxtable
S J
SJ
Kousta
E
E
Jackson
A E
AE
Hattersley
A T
AT
Frayling
T M
TM
Walker
M
M
Kopelman
P G
PG
Ramachandran
A
A
Snehelatha
C
C
Hitman
G A
GA
McCarthy
M I
MI
D000273:Adipose Tissue / Q000033:anatomy & histology*; D000328:Adult; D000483:Alleles; D001208:Asia / Q000208:ethnology; D015992:Body Mass Index; D002352:Carrier Proteins / Q000235:genetics*; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D005060:Europe / Q000208:ethnology; D005260:Female; D006801:Humans; D007194:India / Q000208:ethnology; D007473:Ion Channels; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins; D009679:Nuclear Family; D011110:Polymorphism, Genetic; D015995:Prevalence; D000071247:Uncoupling Protein 3; D006113:United Kingdom / Q000453:epidemiology; D014505:Urban Population / Q000706:statistics & numerical data
D002352:Carrier Proteins; D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604392:UCP3 protein, human; D000071247:Uncoupling Protein 3