A genome-wide scan for human obesity genes reveals a major susceptibility locus on chromosome 10
A genome-wide scan for human obesity genes reveals a major susceptibility locus on chromosome 10
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DOI：
10.1038/3123
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发表时间：
1998-11-01
期刊：
影响因子：
30.8
通讯作者：
Froguel, P
中科院分区：
文献类型：
--
作者：
Hager, J;Dina, C;Froguel, P
肥胖是一种常见的多因素疾病，是2型糖尿病、高血压和冠心病（CHD）的主要危险因素。根据世界卫生组织（WHO）的定义，西方化国家约有6-10%的人口被认为是肥胖(2)。流行病学研究表明，30-70%的体重变化可归因于遗传因素。迄今为止，两次使用不同肥胖相关数量性状的全基因组扫描已经提供了肥胖的候选区域（3,4）。我们对受影响的兄弟姐妹进行了全基因组扫描，以确定与法国家庭肥胖相关的染色体区域。无模型多点连锁分析显示了与染色体10p上一个区域的连锁（MLS=4.85）。染色体5cenq和2p上的另外两个位点显示了血清瘦素水平在全基因组范围内的联系。2号染色体上的峰值与含有编码前阿片素-羊毛皮质素的基因（POMC）的区域一致，该基因位点先前与墨西哥裔美国人的瘦素水平和脂肪量有关(3)，并显示在肥胖人群中发生突变(5)。我们的研究结果表明，染色体10p上有一个主要基因与人类肥胖的发展有关，另外还有两个基因座影响瘦素水平。
Obesity, a common multifactorial disorder, is a major risk factor for type 2 diabetes, hypertension and coronary heart disease(1) (CHD). According to the definition of the World Health Organization (WHO), approximately 6-10% of the population in Westernized countries are considered obese(2). Epidemiological studies have shown that 30-70% of the variation in body weight may be attributable to genetic factors. To date, two genome-wide scans using different obesity-related quantitative traits have provided candidate regions for obesity(3,4). We have undertaken a genome-wide scan in affected sibpairs to identify chromosomal regions linked to obesity in a collection of French families. Model-free multipoint linkage analyses revealed evidence for linkage to a region on chromosome 10p (MLS=4.85). Two further loci on chromosomes 5cen-q and 2p showed suggestive evidence for linkage of serum leptin levels in a genome-wide context. The peak on chromosome 2 coincided with the region containing the gene (POMC) encoding pro-opiome-lanocortin, a locus previously linked to leptin levels and fat mass in a Mexican-American population(3) and shown to be mutated in obese humans(5). Our results suggest that there is a major gene on chromosome 10p implicated in the development of human obesity, and the existence of two further loci influencing leptin levels.