A rare mutation in AgRP, +79G>A, affects promoter activity.
A rare mutation in AgRP, +79G>A, affects promoter activity.
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AgRP 中的罕见突变 79G>A 会影响启动子活性。
DOI：
10.1038/sj.ejcn.1602585
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发表时间：
2007
影响因子：
4.7
通讯作者：
Argyropoulos,G
中科院分区：
文献类型：
--
作者：
Sozen,MA;deJonge,LHM;Greenway,F;Ravussin,E;Smith,SR;Argyropoulos,G
刺豚鼠相关蛋白是一种强有力的促食欲肽。在两个白色携带者的最小启动子中发现了一个罕见的突变，+79 G> A。45岁的男性先证者，也是常见的Ala67Thr多态性的携带者，与年龄和体重匹配的野生型人群进行比较，显示静息代谢率（RMR）和体重指数的边缘差异。然而，第二个携带者是一名肥胖的57岁女性，RMR降低。下丘脑和外周来源的细胞系的功能分析显示，在肾上腺皮质细胞中的+79A等位基因的启动子活性降低，这表明它可以影响外周表达水平的AgRP。+79G> A突变可能使体重增加（如第二携带者的表型所示），但它只会影响年龄较大的先证者，因为他可能受到Ala67Thr多态性的保护，该多态性与抵抗迟发型肥胖有关。
The agouti-related protein is a powerful orexigenic peptide. A rare mutation,+ 79G> A, was identified in its minimal promoter in two white carriers. Comparison of the 45-year-old male proband, who was also a carrier of the common Ala67Thr polymorphism, with an age-and weight-matching wild-type population showed marginal differences for resting metabolic rate (RMR) and body mass index. The second carrier however was an obese 57-year-old female with reduced RMR. Functional analysis in hypothalamus-and periphery-derived cell lines showed reduced promoter activity for the+ 79A allele in the adrenocortical cells only, suggesting that it could affect the peripheral expression levels of AgRP. The+ 79G> A mutation could predispose to body weight gain (as suggested by the phenotype of the second carrier), but it could only affect the proband at an older age as he may be protected by the Ala67Thr polymorphism that is associated with resistance to late-onset fatness.