LEPR gene polymorphisms: associations with overweight, fat mass and response to diet in women

• Published in: European journal of clinical investigation Vol. 31; no. 5; pp. 398 - 404
• Main Authors: Mammès, O., Aubert, R., Betoulle, D., Péan, F., Herbeth, B., Visvikis, S., Siest, G., Fumeron, F.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.05.2001; Blackwell; Blackwell Publishing Ltd
• Subjects: Adipose Tissue - metabolism; Adipose Tissue - physiopathology; Adult; Biological and medical sciences; Body Mass Index; Carrier Proteins - genetics; Diet, Reducing; DNA polymorphisms; fat mass; Female; Genotype; Humans; Leptin receptor gene; low calorie diet; Male; Medical sciences; Metabolic diseases; Obesity; Obesity - diet therapy; Obesity - genetics; Obesity - physiopathology; overweight; Polymerase Chain Reaction; Polymorphism, Genetic - genetics; Polymorphism, Single-Stranded Conformational; Receptors, Cell Surface; Receptors, Leptin; Human; Obesity; Statistical analysis; Pathogenesis; Body weight; Nutrition disorder; Receiver; Fat mass; Genetic disease; Overweight; Polymerase chain reaction; Restriction fragment length polymorphism; Gene; Diet; Leptin; Genetics; Influence; Molecular biology; Nutritional status
• ISSN: 0014-2972; 1365-2362
• DOI: 10.1046/j.1365-2362.2001.00843.x

Background In humans, a mutation of the leptin receptor gene (LEPR) leads to a rare obese syndrome of mendelian inheritance. However, obesity in humans results from interactions between genes and environment, mainly nutritional factors. Variations at the LEPR locus could be involved in the regulation of body weight. Design Genetic variations at the LEPR locus were screened in a selection of 30 French overweight subjects by Single Strand Conformation Polymorphism (SSCP) analysis, then an association study between genotypes and obesity phenotypes was performed in 179 French overweight patients recruited from the Nutrition Department of Bichat Hospital in Paris who were prescribed a low calorie diet and in 387 unrelated volunteers (98 overweight, 289 normal weight) drawn from the Stanislas Family Study in Nancy. Results Two new genetic variants were found: T + 70 → C (exon 1) and Asp (A) 96 Asp (G) (exon 4). In Nancy, the T + 70 → C polymorphism was associated with fat mass adjusted for BMI in women (P = 0·025). The genotype and allele frequencies of the Ser (T) 343 Ser (C) polymorphism (exon 9) were significantly different between normal and overweight women, with the T allele being more frequent in the overweight group (T frequency in Nancy, 0·82; in Nancy + Paris, 0·79) than in the normal weight group (0·69; P = 0·017 vs. Nancy overweight, P = 0·003 vs. Nancy + Paris overweight). In women from Nancy, fat mass adjusted for BMI was significantly associated with this polymorphism (P = 0·01). The overweight women carrying the C allele of this polymorphism lost more weight in response to low calorie diet than the non carriers (P = 0·006). Conclusions In women, genetic variations at the LEPR gene level are associated with overweight and fat mass in a cross sectional study and with response to low calorie diet in an intervention study. These results indicate that variations at the leptin receptor locus are associated with common obesity phenotypes and are a part of the polygenic influences on the response to nutritional environment.