OB GENE IN HUMAN OBESITY

描述(摘自申请人的摘要) 最近肥胖研究的发现将肥胖研究提升到了一个新的水平 荷尔蒙瘦素，一种似乎同时调节食欲和能量的蛋白质 支出，以及人类OB基因的鉴定，它编码 瘦素。在我们实验室之前的研究中，我们检测了三个OB基因 微卫星(D7S514、D7S635和D7S1875)在日本血吸虫样本中的多态性 肥胖和非肥胖的人类受试者。我们发现这些标记是 与腰围和臀围、身体质量指数显著相关 (BMI)、体脂百分比和两种特定的饮食行为：何时进食 在压力下，无聊时吃东西。然而，最强有力的联系是 都是焦虑和抑郁。与文献一致的是， 焦虑/抑郁的发现反映在基因与 促甲状腺激素(TSH)，表明该基因调节进食 通过经典的下丘脑-垂体-肾上腺皮质的行为和能量 (HPA)影响心理基础的途径。建议进行的研究 将尝试通过研究以下内容来复制和扩展这些发现 400例新发肥胖者和200例非肥胖者的基因多态性 正在接受芬氟拉明/酚妥拉明治疗肥胖症。血样 样本和评估将在研究开始时和在 6个月的随访，以确定这些标志物是否 与治疗结果和瘦素水平的变化有关， 压力、荷尔蒙和促甲状腺激素。

DESCRIPTION (Taken from the applicant's Abstract) Obesity research was elevated to a new level by the recent discovery of the hormone leptin, a protein that appears to mediate both appetite and energy expenditure, and by the identification of the human OB gene, which encodes leptin. In prior studies at our laboratory we have examined three OB gene microsatellite polymorphisms (D7S514, D7S635 and D7S1875) in samples of obese and non-obese human subjects. We found that these markers were significantly associated with waist and hip measurements, body mass index (BMI), percent body fat, and two specific eating behaviors: eating when under stress, and eating when bored. However, the most robust associations were with anxiety and depression. Consistent with the literature, the anxiety/depression findings were mirrored by a genetic association with thyroid stimulating hormone (TSH), suggesting that this gene mediates eating behavior and energy via classical hypothalamic-pituitary-adrenocortical (HPA) pathways that influence psychological substrates. The proposed study will attempt to replicate and extend these findings by examining these polymorphisms in 400 new cases of obese and non-obese subjects, 200 of whom are undergoing fenfluramine/phenteramine treatment for obesity. Blood samples and assessments will be obtained both at entry to the study and at 6-month follow-up, in order to determine whether these markers are associated with treatment outcome and with changes in levels of leptin, stress, hormones and TSH.