Hinney A, Bornscheuer A, Depenbusch M, Mierke B, Tölle A, Middeke K, Ziegler A, Roth H, Gerber G, Zamzow K, Ballauff A, Hamann A, Mayer H, Siegfried W, Lehmkuhl G, Poustka F, Schmidt M H, Hermann H, Herpertz-Dahlmann B M, Fichter M, Remschmidt H, Hebebrand J
Department of Child and Adolescent Psychiatry, University of Marburg, Germany.
Mol Psychiatry. 1998 Nov;3(6):539-43. doi: 10.1038/sj.mp.4000394.
Mutations in the leptin gene can result in profound obesity in both rodents and humans. In humans, serum leptin levels correlate with body mass index (BMI: kg m(-2)). However, in patients with anorexia nervosa (AN) leptin levels are lower than in BMI-matched healthy controls. We had previously argued that genes involved in weight regulation should be considered as candidate genes for AN. 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.
瘦素基因的突变可导致啮齿动物和人类出现严重肥胖。在人类中，血清瘦素水平与体重指数（BMI：千克/米²）相关。然而，神经性厌食症（AN）患者的瘦素水平低于体重指数匹配的健康对照者。我们之前曾提出，参与体重调节的基因应被视为AN的候选基因。为了研究这一假设，我们对49例AN患者以及315例极度肥胖的儿童和青少年的瘦素基因编码区和部分瘦素基因上游连接区（LEGLUR）进行了筛查。在编码区发现了两个新的突变（Ser-91-Ser；Glu-126-Gln），每个突变仅在一个先证者中发现，并且在LEGLUR中发现了一个新的多态性（位置-1387 G/A；两个等位基因的频率均约为0.50）。通过比较115例AN患者、71例神经性贪食症患者、315例极度肥胖的儿童和青少年、141例健康体重过低者以及50例未按体重选择的对照者之间的等位基因频率，LEGLUR多态性等位基因的关联测试结果为阴性。传递不平衡测试结果也为阴性。因此，未检测到瘦素基因变异对饮食失调或极早发性肥胖的影响。
