Mutations in the translated part of the leptin gene (LEP) have been found in only two families.
Nevertheless DNA polymorphisms in the LEP region are linked to extreme obesity. We previously
found in the 5′ region of LEP a polymorphism, G-2548A, associated with a difference in BMI
reduction following a low calorie diet in overweight women. Recently, this polymorphism was
associated with extreme obesity in women. In this work, we genotyped a new sample from the
general population including 314 normal weight (BMI < 27 kg/m2) and 109 overweight subjects
(BMI [ges ] 27 kg/m2). The genotype and allele frequencies were significantly different between groups,
with the G-2548 allele being more frequent in the overweight subjects (p < 0.01). In men, carriers of
this allele had lower leptin concentrations adjusted for fat mass (p = 0.05). Our results indicate that
variations at the leptin locus are associated with common obesity phenotypes, and not only with
extreme obesity or the rare mendelian obesity syndromes.