Mercader J M, Ribasés M, Gratacòs M, González J R, Bayés M, de Cid R, Badía A, Fernández-Aranda F, Estivill X
Genes and Disease Program, Center for Genomic Regulation, Barcelona Biomedical Research Park, Barcelona, Catalonia, Spain.
Genes Brain Behav. 2007 Nov;6(8):706-16. doi: 10.1111/j.1601-183X.2007.00301.x. Epub 2007 Mar 21.
Murine models and association studies in eating disorder (ED) patients have shown a role for the brain-derived neurotrophic factor (BDNF) in eating behavior. Some studies have shown association of BDNF -270C/T single-nucleotide polymorphism (SNP) with bulimia nervosa (BN), while BDNF Val66Met variant has been shown to be associated with both BN and anorexia nervosa (AN). To further test the role of this neurotrophin in humans, we screened 36 SNPs in the BDNF gene and tested for their association with ED and plasma BDNF levels as a quantitative trait. We performed a family-based association study in 106 ED nuclear families and analyzed BDNF blood levels in 110 ED patients and in 50 sib pairs discordant for ED. The rs7124442T/rs11030102C/rs11030119G haplotype was found associated with high BDNF levels (mean BDNF TCG haplotype carriers = 43.6 ng/ml vs. mean others 23.0 ng/ml, P = 0.016) and BN (Z = 2.64; P recessive = 0.008), and the rs7934165A/270T haplotype was associated with AN (Z =-2.64; P additive = 0.008). The comparison of BDNF levels in 50 ED discordant sib pairs showed elevated plasma BDNF levels for the ED group (mean controls = 41.0 vs. mean ED = 52.7; P = 0.004). Our data strongly suggest that altered BDNF levels modulated by BDNF gene variability are associated with the susceptibility to ED, providing physiological evidence that BDNF plays a role in the development of AN and BN, and strongly arguing for its involvement in eating behavior and body weight regulation.
小鼠模型及对饮食失调（ED）患者的关联研究表明，脑源性神经营养因子（BDNF）在饮食行为中发挥作用。一些研究显示BDNF -270C/T单核苷酸多态性（SNP）与神经性贪食症（BN）有关，而BDNF Val66Met变异体已被证明与BN和神经性厌食症（AN）均有关联。为了进一步检验这种神经营养因子在人类中的作用，我们筛查了BDNF基因中的36个SNP，并检测它们与ED及作为数量性状的血浆BDNF水平之间的关联。我们在106个ED核心家庭中进行了基于家系的关联研究，并分析了110例ED患者以及50对ED不一致的同胞对的BDNF血药浓度。发现rs7124442T/rs11030102C/rs11030119G单倍型与高BDNF水平（平均BDNF TCG单倍型携带者 = 43.6 ng/ml，而其他平均为23.0 ng/ml，P = 0.016）及BN相关（Z = 2.64；P隐性 = 0.008），且rs7934165A/270T单倍型与AN相关（Z = -2.64；P加性 = 0.008）。对50对ED不一致的同胞对的BDNF水平比较显示，ED组的血浆BDNF水平升高（平均对照组 = 41.0，而平均ED组 = 52.7；P = 0.004）。我们的数据强烈表明，由BDNF基因变异性调节的BDNF水平改变与ED易感性相关，提供了BDNF在AN和BN发展中起作用的生理学证据，并有力地证明其参与饮食行为和体重调节。
