CIBER en Epidemiología y Salud Pública (CIBERESP), Genes and Disease Program, Center for Genomic Regulation (CRG-UPF), Barcelona, Catalonia, Spain.
J Psychiatr Res. 2010 Oct;44(13):834-40. doi: 10.1016/j.jpsychires.2010.01.009. Epub 2010 Mar 9.
Eating disorders (ED) are severe psychiatric diseases that most likely result from, and are sustained by socio-cultural, psychological and biological factors. We explored whether members of the neurotrophin family are disease-modifying factors of quantitative traits, potentially contributing to the outcome or prognosis of the disease. We studied lifetime minimum and maximum body mass index (minBMI and maxBMI) and age at onset of the disease in a sample of 991 ED patients from France, Germany, Italy and Spain and analysed 183 genetic variants located in 10 candidate genes encoding different neurotrophins and their receptors. We used a hierarchical model approach to include prior genetic knowledge of the specific and found that variants in CNTF, in its receptor CNTFR, and in NTRK2 were significantly associated with a lower age at onset of the ED. In addition, one variant in NTRK1 was associated with a higher minBMI. The results suggest that for these two subphenotypes, CNTF, CNTFR, NTRK1 and NTRK2 might act as disease-modifying factors and add preliminary evidence to the global hypothesis that EDs are the result of complex interactions and reciprocal controls between the immune, endocrine and central nervous systems.
饮食失调(ED)是严重的精神疾病,很可能是由社会文化、心理和生物因素引起并维持的。我们探讨了神经营养因子家族成员是否是定量特征的疾病修饰因素,是否有助于疾病的结果或预后。我们研究了来自法国、德国、意大利和西班牙的 991 名 ED 患者的终生最低和最高体重指数(minBMI 和 maxBMI)和发病年龄,并分析了位于 10 个候选基因中的 183 个遗传变异,这些基因编码不同的神经营养因子及其受体。我们使用分层模型方法纳入了特定的遗传先验知识,发现 CNTF、其受体 CNTFR 和 NTRK2 中的变异与 ED 的发病年龄较小显著相关。此外,NTRK1 中的一个变异与 minBMI 较高相关。这些结果表明,对于这两个亚表型,CNTF、CNTFR、NTRK1 和 NTRK2 可能作为疾病修饰因素,并为 ED 是免疫、内分泌和中枢神经系统之间复杂相互作用和相互控制的结果的总体假设提供初步证据。