Association of the G-2548A polymorphism in the 5 ' region of the LEP gene with overweight

Mutations in the translated part of the leptin gene (LEP) hare been found i n only two families. Nevertheless: DNA polymorphisms in the LEP region are linked to extreme obesity. Vile previously found in the 5' region of LEP a polymorphism G-2548A; associated with a difference in BMI reduction followi ng a lon calorie diet in overweight nomen. Recently, this polymorphism was associated with extreme obesity in women. In this work, ise genotyped a new sample from the general population including 314 normal weight (BMI < 27 k g/m(2)) and 109 overweight subjects (BMI <greater than or equal to> 27 kg/m (2)). The genotype and allele frequencies were significantly different betw een groups, with the G-2548 allele being more frequent in the overweight su bjects (p < 0.01). In men, carriers of this allele had lon cr leptin concen trations adjusted for fat mass (p = 0.05). Our results indicate that variat ions at the leptin locus are associated with common obesity phenotypes, and not only with extreme obesity or the rare mendelian obesity syndromes.