Hager J, Dina C, Francke S, Dubois S, Houari M, Vatin V, Vaillant E, Lorentz N, Basdevant A, Clement K, Guy-Grand B, Froguel P
Institut de Biologie de Lille, CNRS EP10, France.
Nat Genet. 1998 Nov;20(3):304-8. doi: 10.1038/3123.
Obesity, a common multifactorial disorder, is a major risk factor for type 2 diabetes, hypertension and coronary heart disease (CHD). According to the definition of the World Health Organization (WHO), approximately 6-10% of the population in Westernized countries are considered obese. 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. 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-opiomelanocortin, a locus previously linked to leptin levels and fat mass in a Mexican-American population and shown to be mutated in obese humans. 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.
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，西方国家约6-10%的人口被认为肥胖。流行病学研究表明，30-70%的体重变化可能归因于遗传因素。迄今为止，两项使用不同肥胖相关数量性状的全基因组扫描提供了肥胖的候选区域。我们对受影响的同胞对进行了全基因组扫描，以在一组法国家庭中确定与肥胖相关的染色体区域。无模型多点连锁分析显示与10号染色体p臂上的一个区域存在连锁证据（MLS=4.85）。在全基因组范围内，5号染色体着丝粒-q臂和2号染色体上的另外两个位点显示出血清瘦素水平连锁的提示性证据。2号染色体上的峰值与包含编码阿黑皮素原的基因（POMC）的区域重合，该位点先前在墨西哥裔美国人中与瘦素水平和脂肪量相关，并在肥胖人群中显示出突变。我们的结果表明，10号染色体p臂上存在一个与人类肥胖发生相关的主要基因，以及另外两个影响瘦素水平的位点。
