OB GENE IN HUMAN OBESITY

描述（摘自申请人摘要） 肥胖症的研究被提升到一个新的水平，最近发现， 瘦素是一种调节食欲和能量的蛋白质 支出，并通过鉴定人OB基因，其编码 瘦素 在我们实验室先前的研究中，我们检测了三个OB基因， 微卫星多态性（D 7S 514，D 7S 635和D 7S 1875）， 肥胖和非肥胖人类受试者。 我们发现这些标记 与腰围、臀围、体重指数 (BMI)，体脂百分比，以及两种特定的饮食行为： 在压力下，无聊的时候吃东西。 然而，最强大的关联 患有焦虑和抑郁症。 与文献一致， 焦虑/抑郁症的发现反映在与以下疾病的遗传关联上： 促甲状腺激素（TSH），表明该基因介导进食 行为和能量通过经典的下丘脑-垂体-肾上腺皮质 (HPA)影响心理基质的途径。 拟定研究 我将尝试通过检查这些， 在400例肥胖和非肥胖受试者的新病例中， 正在接受芬氟拉明/苯海拉明治疗肥胖症。 血液 将在入组研究时和 6-一个月的随访，以确定这些标志物是否 与治疗结果和瘦素水平的变化相关， 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.