Obesity and the brain a possible genetic link 英文参考文献.docVIP

Bertram and Heekeren Alzheimer’s Research Therapy 2010,2:27 /content/2/5/27 COMMENTARY Obesity and the brain: a possible genetic link Lars Bertram * and Hauke Heekeren 1 2,3 the gene encoding the fat mass and obesity-associated protein (FTO), located on chromosome 16q12.2, corre- late with regional brain volumes as determined by magnetic resonance imaging. Abstract Structural brain de?cits have been repeatedly linked to body mass index and obesity, which itself is controlled by the e?ects of a number of independent genetic loci. One of the most consistently replicated of these putative obesity genes is fat mass and obesity-associated protein (FTO). A recent study by investigators from the Alzheimer’s Disease Neuroimaging Initiative set out to assess whether polymorphisms inFTO are directly correlated with brain volume in a collection of over 200 healthy older individuals. The authors found a modest but signi?cant reduction in brain volume in the frontal and occipital lobes exerted by the sameFTO alleles that also predispose to obesity. Although potentially providing a novel genetic link between obesity and brain structure, the relevance of these ?ndings for normal brain function and disease remains to be determined. is question arose because the same FTO alleles at – highly correlated – SNPs were previously found to show association with elevated body mass index (BMI), a commonly used surrogate measure of adiposity [2-5]. Elevated BMI itself has been reported to correlate with structural brain de? cits – in particular, frontal, temporal, and subcortical atrophy [6] – but no study had previously assessed whether this correlation was driven by genetic variation in the FTO gene. e new data from the ADNI group show that, indeed, the same common SNPs associated with BMI are also associated with a ~10% reduction in brain volume in the front