Genetic variation in the leptin receptor gene, leptin, and weight gain in young Dutch adults.
OBJECTIVE
To investigate the association between leptin levels, polymorphisms in the leptin receptor (LEPR) gene, and weight gain.


METHODS
From two large prospective cohorts in The Netherlands (n = 17,500), we compared the baseline leptin of 259 subjects who had gained an average of 12.6 kg (range 5.5 to 33 kg) with 277 subjects who kept stable weight (range -2.6 to 3.1 kg) after a mean follow-up of 6.8 years. Three polymorphisms in the LEPR gene (Lys109Arg, Gln223Arg, and Lys656Asn) were determined.


RESULTS
Weight gainers had significantly higher baseline leptin levels than those who kept stable weight (odds ratio = 1.27, 95% confidence interval 1.1 to 1.5, per SD increase in log(e)-transformed leptin). Weight gainers with the Arg109 or the Arg223 alleles had higher leptin levels compared with the noncarriers of these alleles. Only among men, the association between leptin and weight gain tended to be stronger among those with an Arg223 allele compared with those without this mutation.


CONCLUSIONS
Relatively high leptin levels predict weight gain, suggesting that leptin resistance plays a role in the development of obesity in the general population. Higher leptin levels for those with a Lys109Arg or Gln223Arg mutation (or a linked other marker) may imply that these subjects have a modified functional leptin receptor. However, the role of these mutations on weight gain is limited.
van Rossum
Caroline T M
CT
Department of Chronic Diseases Epidemiology, National Institute of Public Health and the Environment, Bilthoven, The Netherlands. caroline.van.rossum@rivm.nl
Hoebee
Barbara
B
van Baak
Marleen A
MA
Mars
Monica
M
Saris
Wim H M
WH
Seidell
Jacob C
JC
D000328:Adult; D000483:Alleles; D001120:Arginine; D015992:Body Mass Index; D005260:Female; D005973:Glutamine; D006801:Humans; D020738:Leptin / Q000097:blood*; D008239:Lysine; D008297:Male; D009426:Netherlands; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D011956:Receptors, Cell Surface / Q000235:genetics*; D054411:Receptors, Leptin; D012727:Sex Characteristics; D015430:Weight Gain
C515448:LEPR protein, human; D020738:Leptin; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D005973:Glutamine; D001120:Arginine; D008239:Lysine