O'Rahilly Stephen, Farooqi I Sadaf, Yeo Giles S H, Challis Benjamin G
University Department of Medicine, Cambridge Institute of Medical Research, Addenbrooke's Hospital, Cambridge CB2 2QQ, United Kingdom.
Endocrinology. 2003 Sep;144(9):3757-64. doi: 10.1210/en.2003-0373.
Genetic influences on the determination of human fat mass are profound and powerful, a statement that does not conflict with the obvious influence of environmental factors that drive recent changes in the prevalence of obesity. The assertion of the importance of genetic factors has, until recently, largely been based on twin and adoption studies. However, in the last 6 yr, a number of human genes have been identified in which major missense or nonsense mutations are sufficient in themselves to result in severe early-onset obesity, usually associated with disruption of normal appetite control mechanisms. Progress in the identification of more common, subtler genetic variants that influence fat mass in larger numbers of people has been slower, but discernible. Human genetics will continue to make an invaluable contribution to the study of human obesity by identifying critical molecular components of the human energy balance regulatory systems, pointing the way toward more targeted and effective therapies and assisting the prediction of individual responses to environmental manipulations.
基因对人体脂肪量的决定作用是深远且强大的，这一说法与驱动近期肥胖患病率变化的环境因素的明显影响并不冲突。直到最近，关于基因因素重要性的论断很大程度上是基于双胞胎和收养研究。然而，在过去6年里，已经鉴定出一些人类基因，其中主要的错义或无义突变本身就足以导致严重的早发性肥胖，通常还伴有正常食欲控制机制的紊乱。在鉴定影响更多人脂肪量的更常见、更细微的基因变体方面进展较慢，但仍可察觉。通过识别人类能量平衡调节系统的关键分子成分，为更有针对性和有效的治疗指明方向，并协助预测个体对环境干预的反应，人类遗传学将继续为人类肥胖研究做出宝贵贡献。
