将近半数西欧人携带的一种与肥胖有关的基因变异可能也与大脑退化有联系。Paul Thompson及其同事生成了200多位健康的老年白人受试者的大脑3D图，结果发现了“与脂肪和肥胖相关”基因内的一种特定的DNA序列的携带者比非携带者表现出了大脑容量减少的模式。这种大脑差异可能无法直接归结于其它肥胖相关因素，例如胆固醇水平、糖尿病或高血压。此前的研究发现46%的西欧和中欧人以及16%的亚洲人携带这种与高于平均水平的体重和腰围有关的等位基因。肥胖是认知功能衰退的已知风险因素，而且此前科学家已经把它和超重人群脑容量的可探测差异联系了起来。这组作者说，这项研究并没有发现这种等位基因携带者的脑萎缩的机制，而且也无法确定这种DNA序列的遗传影响是否处于决定肥胖的因素之中。这组科学家提出，这种遗传变异可能超出体重影响的大脑退化有贡献。
论文 #09-10878: “A commonly carried allele of the obesity-related FTO gene is associated with reduced brain volume in healthy elderly," 作者April Ho, Jason Stein, Xue Hua, Suh Lee, Derrek Hibar, Alex Leow, Ivo Dinov, Arthur Toga, Andrew Saykin, Li Shen, Tatiana Foroud, Nathan Pankratz, Matthew Huentelman, David Craig, Jill Gerber, April Allen, Jason Corneveaux, Dietrich Stephan, Charles DeCarli, Bryan DeChairo, Steven Potkin, Clifford Jack, Michael Weiner, Cyrus Raji, Oscar Lopez, James Becker, Owen Carmichael和 Paul Thompson
媒体联系人：Paul Thompson，加州大学洛杉矶分校神经病学系
Department, Department of Neurology, University of California, Los Angeles, Los Angeles, CA
电话：310-206-2101
电子邮件：thompson@loni.ucla.edu
Published online before print April 19, 2010, doi: 10.1073/pnas.0910878107
Abstract
A recently identified variant within the fat mass and obesity-associated (FTO) gene is carried by 46% of Western Europeans and is associated with an ~1.2 kg higher weight, on average, in adults and an ~1 cm greater waist circumference. With <1 billion overweight and 300 million obese persons worldwide, it is crucial to understand the implications of carrying this very common allele for the health of our aging population. FTO is highly expressed in the brain and elevated body mass index (BMI) is associated with brain atrophy, but it is unknown how the obesity-associated risk allele affects human brain structure. We therefore generated 3D maps of regional brain volume differences in 206 healthy elderly subjects scanned with MRI and genotyped as part of the Alzheimer's Disease Neuroimaging Initiative. We found a pattern of systematic brain volume deficits in carriers of the obesity-associated risk allele versus noncarriers. Relative to structure volumes in the mean template, FTO risk allele carriers versus noncarriers had an average brain volume difference of ~8% in the frontal lobes and 12% in the occipital lobes—these regions also showed significant volume deficits in subjects with higher BMI. These brain differences were not attributable to differences in cholesterol levels, hypertension, or the volume of white matter hyperintensities; which were not detectably higher in FTO risk allele carriers versus noncarriers. These brain maps reveal that a commonly carried susceptibility allele for obesity is associated with structural brain atrophy, with implications for the health of the elderly.
