Loos R J F, Bouchard C
Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.
J Intern Med. 2003 Nov;254(5):401-25. doi: 10.1046/j.1365-2796.2003.01242.x.
Obesity is one of the most pressing problems in the industrialized world. Twin, adoption and family studies have shown that genetic factors play a significant role in the pathogenesis of obesity. Rare mutations in humans and model organisms have provided insights into the pathways involved in body weight regulation. Studies of candidate genes indicate that some of the genes involved in pathways regulating energy expenditure and food intake may play a role in the predisposition to obesity. Amongst these genes, sequence variations in the adrenergic receptors, uncoupling proteins, peroxisome proliferator-activated receptor, and the leptin receptor genes are of particular relevance. Results that have been replicated in at least three genome-wide scans suggest that key genes are located on chromosomes 2p, 3q, 5p, 6p, 7q, 10p, 11q, 17p and 20q. We conclude that the currently available evidence suggests four levels of genetic determination of obesity: genetic obesity, strong genetic predisposition, slight genetic predisposition, and genetically resistant. This growing body of research may help in the development of anti-obesity agents and perhaps genetic tests to predict the risk for obesity.
肥胖是工业化世界中最紧迫的问题之一。双胞胎、收养及家族研究表明，遗传因素在肥胖的发病机制中起着重要作用。人类和模式生物中的罕见突变已为体重调节所涉及的途径提供了见解。对候选基因的研究表明，一些参与能量消耗和食物摄入调节途径的基因可能在肥胖易感性中起作用。在这些基因中，肾上腺素能受体、解偶联蛋白、过氧化物酶体增殖物激活受体和瘦素受体基因的序列变异尤为相关。至少在三次全基因组扫描中得到重复的结果表明，关键基因位于2号染色体短臂、3号染色体长臂、5号染色体短臂、6号染色体短臂、7号染色体长臂、10号染色体短臂、11号染色体长臂、17号染色体短臂和20号染色体长臂上。我们得出结论，目前可得的证据表明肥胖存在四个遗传决定水平：遗传性肥胖、强遗传易感性、弱遗传易感性和遗传抗性。这一不断增加的研究成果可能有助于抗肥胖药物的研发，或许还能用于开发预测肥胖风险的基因检测。
