Association between an agouti-related protein gene polymorphism and anorexia nervosa
Association between an agouti-related protein gene polymorphism and anorexia nervosa
复制标题
DOI：
10.1038/sj.mp.4000854
复制
发表时间：
2001-05-01
影响因子：
11
通讯作者：
Adan, RAH
中科院分区：
文献类型：
--
作者：
Vink, T;Hinney, A;Adan, RAH
神经性厌食症（AN）是一种威胁生命的疾病，主要影响青少年女性。这是一种严重的精神综合征，伴有严重的体重减轻、多动和神经内分泌变化（综述见参考文献1和2）。几项研究表明AN中有很强的遗传成分（参考文献3）。在阐明体重控制机制方面的最新进展（4）指出了黑皮质素-4受体（MC 4-r）系统在调节体重中的关键作用。食欲神经肽agouti-related蛋白（AGRP），MC 4-r拮抗剂，在维持体重，诱导食物摄入中起着至关重要的作用。测定了人AGRP基因编码区（AGRP）的序列，并对100例AN患者的AGRP进行了变异筛查。在另外45名患者和244名对照中确定并筛选了三种单核苷酸多态性（SNPs）。两个等位基因完全连锁不平衡，显着富集厌食症患者（11%; P = 0.015）相比，对照组（4.5%）。这些数据表明AGRP的变化与AN的易感性有关。这可能是由变体AGRP对MC 4-r的抑制缺陷引起的，导致进食信号降低，增加了发展AN的风险。这些结果暗示，MC 4-r的拮抗作用可被认为是AN患者的药物治疗。
Anorexia nervosa (AN) is a life threatening disorder affecting mostly adolescent women. It is a dramatic psychiatric syndrome accompanied by severe weight loss, hyperactivity and neuroendocrine changes (reviewed in Refs 1 and 2). Several studies have shown a strong genetic component in AN (reviewed in Ref 3). Recent advances in unraveling the mechanisms of weight control(4) point to a crucial role of the melanocortin-4 receptor (MC4-r) system in regulating body weight. The orexigenic neuropeptide agouti-related protein (AGRP), a MC4-r antagonist, plays a crucial role in maintaining body weight, by inducing food intake. The sequence of the coding region of the human AGRP gene (AGRP) was determined and the AGRP of 100 patients with AN was screened for variations. Three single nucleotide polymorphisms (SNPs) were identified and screened in a further 45 patients and 244 controls. Two alleles were in complete linkage disequilibrium and were significantly enriched in anorectic patients (11%; P = 0.015) compared to controls (4.5%). These data indicate that variations of AGRP are associated with susceptibility for AN. This is possibly caused by defective suppression of the MC4-r by the variant AGRP, leading to a decreased feeding signal, increasing the risk of developing AN. These results implicate that antagonism of the MC4-r might be considered as pharmacotherapy for patients with AN.