A polymorphism in the human agouti-related protein is associated with late-onset obesity
A polymorphism in the human agouti-related protein is associated with late-onset obesity
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DOI：
10.1210/jc.2002-011834
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发表时间：
2002-09-01
影响因子：
5.8
通讯作者：
Bouchard, C
中科院分区：
文献类型：
--
作者：
Argyropoulos, G;Rankinen, T;Bouchard, C
小鼠刺豚鼠相关蛋白（AGRP）是一种强大的食欲效应子，当脑室内给药或在转基因小鼠中过表达时，会导致食欲过旺和肥胖的发展。动物研究还表明，外源性AGRP给药倾向于高脂肪和高糖饮食的享乐摄入。人类直系同源物（hAGRP）定位在染色体16 q22上，并且具有类似的生理特性，如在动物模型中测试的。在hAGRP的第三个外显子中发现了多态性，c.199G --> A，导致非保守性氨基酸取代，Ala（67）Thr。蛋白质的计算分析表明，显着差异的线圈的两个多态性异构体的蛋白质。人类研究表明，在平均年龄为25岁的个体中没有基因型效应。然而，在平均年龄为53岁的父母群体中，GIG基因型与肥胖和腹部肥胖显著相关。因此，hAGRP的c.199G --> A多态性可能以年龄依赖性的方式在人类肥胖的发展中发挥作用。
The mouse agouti-related protein (AGRP) is a powerful appetite effector that results in hyperphagia and the development of obesity when administered intracerebroventricularly or when overexpressed in transgenic mice. Animal studies have also shown that exogenous administration of AGRP predisposes toward hedonic intake of high fat and high sucrose diets. The human ortholog (hAGRP) maps on chromosome 16q22 and has similar physiological properties, as tested in animal models. A polymorphism was identified in the third exon of hAGRP, c.199G --> A, that resulted in a nonconservative amino acid substitution, Ala(67)Thr. Computational analysis of the protein showed significant differences in the coils of the two polymorphic isoforms of the protein. Human studies showed no genotype effects in individuals with a mean age of 25 yr. However, the GIG genotype was significantly associated with fatness and abdominal adiposity in the parental population with a mean age of 53 yr. The c.199G --> A polymorphism in hAGRP could, therefore, play a role in the development of human obesity in an age-dependent fashion.