Ribasés Marta, Gratacòs Mònica, Fernández-Aranda Fernando, Bellodi Laura, Boni Claudette, Anderluh Marija, Cristina Cavallini Maria, Cellini Elena, Di Bella Daniela, Erzegovesi Stefano, Foulon Christine, Gabrovsek Mojca, Gorwood Philip, Hebebrand Johannes, Hinney Anke, Holliday Jo, Hu Xun, Karwautz Andreas, Kipman Amélie, Komel Radovan, Nacmias Benedetta, Remschmidt Helmut, Ricca Valdo, Sorbi Sandro, Tomori Martina, Wagner Gudrun, Treasure Janet, Collier David A, Estivill Xavier
Genes and Disease Program, Center for Genomic Regulation, Barcelona Biomedical Research Park, Barcelona, Spain.
Eur J Hum Genet. 2005 Apr;13(4):428-34. doi: 10.1038/sj.ejhg.5201351.
Eating disorders (ED), such as anorexia nervosa (AN) and bulimia nervosa (BN), are complex psychiatric disorders where different genetic and environmental factors are involved. Several lines of evidence support that brain-derived neurotrophic factor (BDNF) plays an essential role in eating behaviour and that alterations on this neurotrophic system participates in the susceptibility to both AN and BN. Accordingly, intraventricular administration of BDNF in rats determines food starvation and body weight loss, while BDNF or its specific receptor NTRK2 knockout mice develop obesity and hyperphagia. Case-control studies also suggest a BDNF contribution in the aetiology of ED: we have previously reported a strong association between the Met66 variant within the BDNF gene, restricting AN (ANR) and minimum body mass index (minBMI) in a Spanish sample, and a positive association between the Val66Met and -270C/T BDNF SNPs and ED in six different European populations. To replicate these results, avoiding population stratification effects, we recruited 453 ED trios from eight European centres and performed a family-based association study. Both haplotype relative risk (HRR) and haplotype-based haplotype relative risk (HHRR) methods showed a positive association between the Met66 allele and ANR. Consistently, we also observed an effect of the Met66 variant on low minBMI and a preferential transmission of the -270C/Met66 haplotype to the affected ANR offspring. These results support the involvement of BDNF in eating behaviour and further suggest its participation in the genetic susceptibility to ED, mainly ANR and low minBMI.
饮食失调（ED），如神经性厌食症（AN）和神经性贪食症（BN），是复杂的精神疾病，涉及不同的遗传和环境因素。多条证据支持脑源性神经营养因子（BDNF）在饮食行为中起重要作用，并且这种神经营养系统的改变参与了AN和BN的易感性。相应地，在大鼠脑室内注射BDNF会导致食物饥饿和体重减轻，而BDNF或其特异性受体NTRK2基因敲除小鼠会出现肥胖和食欲亢进。病例对照研究也表明BDNF在ED的病因学中起作用：我们之前报道过，在一个西班牙样本中BDNF基因内的Met66变体、限制性AN（ANR）和最低体重指数（minBMI）之间存在强关联，并且在六个不同的欧洲人群中，Val66Met和-270C/T BDNF单核苷酸多态性（SNP）与ED之间存在正相关。为了重复这些结果并避免人群分层效应，我们从八个欧洲中心招募了453个ED三联体，并进行了基于家系的关联研究。单倍型相对风险（HRR）和基于单倍型的单倍型相对风险（HHRR）方法均显示Met66等位基因与ANR之间存在正相关。一致地，我们还观察到Met66变体对低minBMI有影响，并且-270C/Met66单倍型优先传递给受影响的ANR后代。这些结果支持BDNF参与饮食行为，并进一步表明其参与了ED的遗传易感性，主要是ANR和低minBMI。
