Association of insulin-like growth factor-1 receptor polymorphism in dementia
Association of insulin-like growth factor-1 receptor polymorphism in dementia
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DOI：
10.1159/000095803
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发表时间：
2006-01-01
影响因子：
2.4
通讯作者：
Marcusson, J.
中科院分区：
文献类型：
--
作者：
Garcia, J.;Ahmadi, A.;Marcusson, J.
人们越来越关注氧化应激如何导致细胞在正常衰老和神经退行性疾病中发生凋亡。先前的研究表明胰岛素样生长因子-1（IGF-1）通过降低神经元对氧化应激的敏感性来保护神经元，从而参与阿尔茨海默病（AD）的发病机制。IGF-1受体（IGF-1 R）多态性改变大脑和全身IGF-1水平，并可能改变受体的功能。我们通过聚合酶链反应（PCR）和限制性片段长度多态性（RFLP）对IGF-1 R基因进行基因分型，以评估该基因多态性是否与痴呆症相关。我们使用了72例AD患者，75例血管性痴呆（VaD）患者，14例混合性痴呆（AD+VaD）患者的白细胞DNA，以及由209名无进行性神经系统疾病史的个体组成的对照组。性别的基因频率分析显示，女性VaD患者和携带至少一个A等位基因的女性对照之间存在显著差异（OR = 1.8，CI 95% 1.1 - 2.9，p = 0.02），但男性患者无显著差异。此外，我们发现所有携带A等位基因的女性痴呆患者和对照组之间存在差异的强烈趋势（OR = 1.5，CI 95% 0.99 - 2.2，p = 0.054）。提示IGF-1 R的A等位基因可能参与女性VaD的发病。版权所有（C）2006 S. Karger AG，巴塞尔。
There is an increasing interest in how oxidative stress can cause cells to go into apoptosis in both normal ageing and in neurodegenerative disorders. Previous research has implicated insulin-like growth factor-1 (IGF-1) as being involved in the pathogenesis in Alzheimer's disease ( AD) by protecting the neurons through reducing neuronal susceptibility to oxidative stress. IGF-1 receptor (IGF-1R) polymorphisms alter cerebral and systemic levels of IGF-1 and may alter the function of the receptor. We genotyped the IGF-1R gene by polymerase chain reaction (PCR) and restriction fragment length polymorphism ( RFLP) to assess whether this gene polymorphism can be linked to dementia. We used leukocyte DNA from 72 patients with AD, 75 patients with vascular dementia (VaD), 14 patients with mixed dementia (AD+VaD), and a control group consisting of 209 individuals without a history of progressive neurological disorders. Analysis of gene frequency for gender revealed a significant difference between female VaD patients and female controls carrying at least one A allele ( OR = 1.8, CI 95% 1.1 - 2.9, p = 0.02), but not for male patients. In addition, we found a strong tendency to a difference between all cases of female dementia patients and controls carrying the A allele ( OR = 1.5, CI 95% 0.99 - 2.2, p = 0.054). Our results suggest that the A allele of IGF-1R may be involved in the pathogenesis of VaD in females. Copyright (C) 2006 S. Karger AG, Basel.