Genetic polymorphisms and weight loss in obesity: a randomised trial of hypo-energetic high- versus low-fat diets.
OBJECTIVE
To study if genes with common single nucleotide polymorphisms (SNPs) associated with obesity-related phenotypes influence weight loss (WL) in obese individuals treated by a hypo-energetic low-fat or high-fat diet.


METHODS
Randomised, parallel, two-arm, open-label multi-centre trial.


METHODS
Eight clinical centres in seven European countries.


METHODS
771 obese adult individuals.


METHODS
10-wk dietary intervention to hypo-energetic (-600 kcal/d) diets with a targeted fat energy of 20%-25% or 40%-45%, completed in 648 participants.


METHODS
WL during the 10 wk in relation to genotypes of 42 SNPs in 26 candidate genes, probably associated with hypothalamic regulation of appetite, efficiency of energy expenditure, regulation of adipocyte differentiation and function, lipid and glucose metabolism, or production of adipocytokines, determined in 642 participants.


RESULTS
Compared with the noncarriers of each of the SNPs, and after adjusting for gender, age, baseline weight and centre, heterozygotes showed WL differences that ranged from -0.6 to 0.8 kg, and homozygotes, from -0.7 to 3.1 kg. Genotype-dependent additional WL on low-fat diet ranged from 1.9 to -1.6 kg in heterozygotes, and from 3.8 kg to -2.1 kg in homozygotes relative to the noncarriers. Considering the multiple testing conducted, none of the associations was statistically significant.


CONCLUSIONS
Polymorphisms in a panel of obesity-related candidate genes play a minor role, if any, in modulating weight changes induced by a moderate hypo-energetic low-fat or high-fat diet.
Sørensen
Thorkild I A
TI
Institute of Preventive Medicine, Danish Epidemiology Science Centre, Copenhagen University Hospital, Copenhagen, Denmark. tias@ipm.hosp.dk
Boutin
Philippe
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Taylor
Moira A
MA
Larsen
Lesli H
LH
Verdich
Camilla
C
Petersen
Liselotte
L
Holst
Claus
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Echwald
Søren M
SM
Dina
Christian
C
Toubro
Søren
S
Petersen
Martin
M
Polak
Jan
J
Clément
Karine
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Martínez
J Alfredo
JA
Langin
Dominique
D
Oppert
Jean-Michel
JM
Stich
Vladimir
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Macdonald
Ian
I
Arner
Peter
P
Saris
Wim H M
WH
Pedersen
Oluf
O
Astrup
Arne
A
Froguel
Philippe
P