Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen AB24 2TZ, Scotland, UK.
Nature. 2010 Apr 1;464(7289):E1; discussion E2. doi: 10.1038/nature08807.
An intronic single nucleotide polymorphism (SNP) (rs9939609) close to the fat mass and obesity associated gene (FTO) was the first SNP to be discovered with common variants linked to body mass index; at least seven studies in humans have implicated this SNP with variations in food intake and satiety, and four studies have rejected an effect on energy expenditure normalized for body weight. Fischer et al. recently constructed a mouse in which the homologous Fto gene was inactivated (Fto(-/-)) and showed that these mice were protected from obesity. This observation strongly implicates the effects of the intronic SNP rs9939609 as arising due to an effect on the closest gene (FTO). However, the suggested mechanism underlying this effect in mice was opposite to that in humans. The Fto(-/-) mice showed no significant differences in food intake relative to wild-types litter-mates but had an elevated metabolic rate. The apparent contrasting effects of the gene in humans and mice is worthy of closer investigation.
一个位于肥胖相关基因（FTO）附近的内含子单核苷酸多态性（SNP）（rs9939609）是第一个被发现与体重指数相关的常见变异体有关的 SNP；至少有七项人类研究表明该 SNP 与食物摄入和饱腹感的变化有关，四项研究表明其对体重标准化的能量消耗没有影响。Fischer 等人最近构建了一种同源 Fto 基因失活（Fto(-/-)）的小鼠，并表明这些小鼠可以预防肥胖。这一观察结果强烈表明，内含子 SNP rs9939609 的影响是由于对最接近的基因（FTO）的影响所致。然而，在小鼠中这种影响的潜在机制与人类相反。Fto(-/-)小鼠的食物摄入量与野生型同窝仔鼠相比没有显著差异，但代谢率升高。该基因在人类和小鼠中的明显相反作用值得进一步研究。
