Human Molecular Genetics, Vol 6, 869-876, Copyright © 1997 by Oxford University Press
T Gotoda, BS Manning, AP Goldstone, H Imrie, AL Evans, AD Strosberg, PM McKeigue, J Scott and TJ Aitman
Leptin, a hormone secreted by adipocytes, plays a pivotal role in the
control of body weight. Rodents with mutations in the leptin receptor gene
develop morbid obesity. It is possible, therefore, that leptin receptor
gene mutations contribute to human obesity. To test this possibility, we
determined the entire coding sequence of the human leptin receptor cDNA
from peripheral blood lymphocytes of 22 morbidly obese patients with
body-mass index (BMI) between 35.1 and 60.9 kg/m2. We identified five
common DNA sequence variants distributed throughout the coding sequence at
codons 109, 223, 343, 656 and 1019, one rare silent mutation at codon 986
and one novel alternatively spliced form of transcript. None of the five
common variants, including the three that predict amino acid changes, are
null mutations causing morbid obesity, because homozygotes for the variant
sequences were also found in lean subjects. Furthermore, the frequency of
each variant allele and the distribution of genotypes and haplotypes were
similar in 190 obese (BMI >28 kg/m2) and 132 lean (BMI <22 kg/m2)
white British males selected from a population-based epidemiological
survey. In these subjects, there was no evidence for a significant effect
of the common variants on obesity or obesity-related phenotypes. These
results suggest that mutations in the leptin receptor gene are not a common
cause of human obesity.
ARTICLES
Leptin receptor gene variation and obesity: lack of association in a white British male population
MRC Clinical Sciences Centre, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
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