Yilmaz Zeynep, Kaplan Allan S, Tiwari Arun K, Levitan Robert D, Piran Sara, Bergen Andrew W, Kaye Walter H, Hakonarson Hakon, Wang Kai, Berrettini Wade H, Brandt Harry A, Bulik Cynthia M, Crawford Steven, Crow Scott, Fichter Manfred M, Halmi Katherine A, Johnson Craig L, Keel Pamela K, Klump Kelly L, Magistretti Pierre, Mitchell James E, Strober Michael, Thornton Laura M, Treasure Janet, Woodside D Blake, Knight Joanne, Kennedy James L
Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Clinical Research Department, Centre for Addiction and Mental Health, Toronto, Canada.
Clinical Research Department, Centre for Addiction and Mental Health, Toronto, Canada; Institute of Medical Science, University of Toronto, Toronto, Canada; Department of Psychiatry, University of Toronto, Toronto, Canada.
J Psychiatr Res. 2014 Aug;55:77-86. doi: 10.1016/j.jpsychires.2014.04.005. Epub 2014 Apr 16.
Although low weight is a key factor contributing to the high mortality in anorexia nervosa (AN), it is unclear how AN patients sustain low weight compared with bulimia nervosa (BN) patients with similar psychopathology. Studies of genes involved in appetite and weight regulation in eating disorders have yielded variable findings, in part due to small sample size and clinical heterogeneity. This study: (1) assessed the role of leptin, melanocortin, and neurotrophin genetic variants in conferring risk for AN and BN; and (2) explored the involvement of these genes in body mass index (BMI) variations within AN and BN.
Our sample consisted of 745 individuals with AN without a history of BN, 245 individuals with BN without a history of AN, and 321 controls. We genotyped 20 markers with known or putative function among genes selected from leptin, melanocortin, and neurotrophin systems.
There were no significant differences in allele frequencies among individuals with AN, BN, and controls. AGRP rs13338499 polymorphism was associated with lowest illness-related BMI in those with AN (p = 0.0013), and NTRK2 rs1042571 was associated with highest BMI in those with BN (p = 0.0018).
To our knowledge, this is the first study to address the issue of clinical heterogeneity in eating disorder genetic research and to explore the role of known or putatively functional markers in genes regulating appetite and weight in individuals with AN and BN. If replicated, our results may serve as an important first step toward gaining a better understanding of weight regulation in eating disorders.
尽管体重过低是神经性厌食症（AN）高死亡率的关键因素，但与具有相似精神病理学特征的神经性贪食症（BN）患者相比，AN患者如何维持低体重尚不清楚。对饮食失调中涉及食欲和体重调节的基因研究结果不一，部分原因是样本量小和临床异质性。本研究：（1）评估瘦素、黑皮质素和神经营养因子基因变异在AN和BN发病风险中的作用；（2）探讨这些基因在AN和BN患者体重指数（BMI）变化中的作用。
我们的样本包括745例无BN病史的AN患者、245例无AN病史的BN患者和321名对照。我们对从瘦素、黑皮质素和神经营养因子系统中选择的基因中的20个具有已知或推定功能的标记进行了基因分型。
AN患者、BN患者和对照之间的等位基因频率没有显著差异。AGRP rs13338499多态性与AN患者中最低的疾病相关BMI相关（p = 0.0013），NTRK2 rs1042571与BN患者中最高的BMI相关（p = 0.0018）。
据我们所知，这是第一项解决饮食失调基因研究中临床异质性问题，并探讨已知或推定功能标记在调节AN和BN患者食欲和体重的基因中的作用的研究。如果得到重复验证，我们的结果可能是朝着更好地理解饮食失调中的体重调节迈出的重要第一步。
