Abstract
Mutations in the leptin gene can result in profound obesity in both rodents and humans.1–3 In humans, serum leptin levels correlate with body mass index4 (BMI: kg m−2). However, in patients with anorexia nervosa (AN) leptin levels are lower than in BMI-matched healthy controls.5 We had previously argued that genes involved in weight regulation should be considered as candidate genes for AN.6 To investigate this hypothesis we screened the coding region of the leptin gene and part of the leptin gene linked upstream region (LEGLUR) in 49 patients with AN and 315 children and adolescents with extreme obesity. Two novel mutations in the coding region (Ser-91-Ser; Glu-126-Gln), each found in a single proband, and a novel polymorphism in the LEGLUR (position −1387 G/A; frequency of both alleles approximately 0.50) were identified. Tests for association of LEGLUR polymorphism alleles were negative by comparing allele frequencies between 115 AN patients, 71 bulimia nervosa patients, 315 extremely obese children and adolescents, 141 healthy underweights and 50 controls that were not selected for body weight. Tests for transmission disequilibrium were also negative. Hence, an influence of variations in the leptin gene on eating disorders or extreme early onset obesity could not be detected.
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Hinney, A., Bornscheuer, A., Depenbusch, M. et al. No evidence for involvement of the leptin gene in anorexia nervosa, bulimia nervosa, underweight or early onset extreme obesity: identification of two novel mutations in the coding sequence and a novel polymorphism in the leptin gene linked upstream region. Mol Psychiatry 3, 539–543 (1998). https://doi.org/10.1038/sj.mp.4000394
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DOI: https://doi.org/10.1038/sj.mp.4000394
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