Human Molecular Genetics, Vol 7, 435-440, Copyright © 1998 by Oxford University Press
A Meirhaeghe, L Fajas, N Helbecque, D Cottel, P Lebel, J Dallongeville, S Deeb, J Auwerx and P Amouyel
Peroxisome proliferator-activated receptor gamma (PPARgamma) is a
transcription factor implicated in adipocyte differentiation, lipid and
glucose metabolism. A polymorphism corresponding to a silent C-->T
substitution was detected in exon 6 of the PPAR gamma gene. We analysed the
relationships between this genetic polymorphism and various markers of the
obesity phenotype (body weight, body mass index, waist:hip ratio and plasma
leptin levels) in a representative sample of 820 men and women living in
northern France. The frequencies of the C and T alleles were 0.860 and
0.140 respectively. In the whole sample no association of the polymorphism
with the markers tested was observed but a statistically significant
interaction ( P < 0.03) existed between this polymorphism and body mass
index for plasma leptin levels. This result suggested that the impact of
the PPAR gamma gene polymorphism on plasma leptin levels differed according
to the BMI of the subjects. Indeed, obese subjects (BMI >30 kg/m2)
bearing at least one T allele ( CT + TT ) had higher plasma leptin levels
than subjects who did not (35.0 +/- 17.4 ng/ml versus 28.3 +/- 14.8 ng/ml
respectively; P < 0.001). This effect existed in both genders, despite
the higher plasma leptin levels observed in women. The plasma leptin level
increase was not associated with elevation of body mass index, even though
these two variables were highly correlated. Thus for a given leptin level
the BMI was relatively lower in obese subjects carrying at least one T
allele than in obese CC homozygotes. Our results show that in obese
subjects variability within the PPAR gamma gene locus is associated with
circulating leptin levels and may modify the relationship between leptin
levels and adipose tissue mass.
ARTICLES
A genetic polymorphism of the peroxisome proliferator-activated receptor gamma gene influences plasma leptin levels in obese humans
Unite d'Epidemiologie et de Sante Publique, INSERM CJF 95-05, Institut Pasteur de Lille, 1 rue Calmette, 59019 Lille Cedex, France.
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