Mammès O, Aubert R, Betoulle D, Péan F, Herbeth B, Visvikis S, Siest G, Fumeron F
Xavier Bichat Medicine School, Paris, France.
Eur J Clin Invest. 2001 May;31(5):398-404. doi: 10.1046/j.1365-2362.2001.00843.x.
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.
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.
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).
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.
在人类中，瘦素受体基因（LEPR）的突变会导致一种罕见的孟德尔遗传肥胖综合征。然而，人类肥胖是由基因与环境（主要是营养因素）之间的相互作用引起的。LEPR基因座的变异可能参与体重调节。
通过单链构象多态性（SSCP）分析，在30名法国超重受试者中筛选LEPR基因座的遗传变异，然后在从巴黎比沙医院营养科招募的179名接受低热量饮食治疗的法国超重患者以及从南锡斯坦尼斯拉斯家族研究中抽取的387名无关志愿者（98名超重，289名体重正常）中进行基因型与肥胖表型之间的关联研究。
发现了两个新的遗传变异：T + 70→C（外显子1）和Asp（A）96 Asp（G）（外显子4）。在南锡，T + 70→C多态性与女性经体重指数（BMI）校正后的脂肪量相关（P = 0.025）。正常体重和超重女性之间Ser（T）343 Ser（C）多态性（外显子9）的基因型和等位基因频率存在显著差异，超重组中T等位基因的频率高于正常体重组（在南锡，T频率为0.82；在南锡+巴黎，T频率为0.79）（与南锡超重组相比，P = 0.017；与南锡+巴黎超重组相比，P = 0.003）。在南锡的女性中，经BMI校正后的脂肪量与该多态性显著相关（P = 0.01）。携带该多态性C等位基因的超重女性对低热量饮食的反应比非携带者体重减轻更多（P = 0.006）。
在女性中，一项横断面研究表明LEPR基因水平的遗传变异与超重和脂肪量相关，一项干预研究表明其与对低热量饮食的反应相关。这些结果表明，瘦素受体基因座的变异与常见肥胖表型相关，并且是对营养环境反应的多基因影响的一部分。
