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胰岛素样生长因子 1(IGF1)多态性与汉族人群的阿尔茨海默病有关。

Insulin-like growth factor 1 (IGF1) polymorphism is associated with Alzheimer's disease in Han Chinese.

机构信息

Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao 266071, China.

出版信息

Neurosci Lett. 2012 Nov 30;531(1):20-3. doi: 10.1016/j.neulet.2012.10.015. Epub 2012 Oct 23.

Abstract

A review of pathogenic findings in Alzheimer's brains and the functional consequences of altered insulin-like growth factor 1 (IGF1) input to the brain suggest the association between Alzheimer's disease (AD) and the disrupted IGF1 signaling. Recently, the identification of polymorphism rs972936 that was associated with both an increased risk of AD and high circulating levels of IGF1 was reported in Southern European population. In order to evaluate the involvement of the IGF1 polymorphism in the risk of developing late-onset Alzheimer's disease (LOAD) in Chinese, we performed an independent case-control association study in a Han Chinese population (794 LOAD cases and 796 controls). There were significant differences in genotype and allele frequencies between LOAD cases and controls (genotype P = 0.006, allele P = 0.047). The T allele of rs972936 demonstrated a 1.16-fold risk for developing LOAD when compared with the C allele, which diverges to the report in the Caucasian population. After stratification by apolipoprotein E (APOE) ɛ4-carrying status, rs972936 polymorphism was only significantly associated with LOAD in non-ApoE ɛ4 allele carriers (genotype P = 0.002, allele P = 0.039). Multivariate logistic regression analysis also conferred this positive association between the SNP rs972936 and LOAD in the recessive and additive model after adjustment for age, gender, and the ApoE ɛ4 carrier status. These results suggest that IGF1 polymorphism has a possible role in changing the genetic susceptibility to LOAD in a Han Chinese population.

摘要

阿尔茨海默病(AD)与胰岛素样生长因子 1(IGF1)信号通路的改变有关,对 AD 患者大脑中的致病发现和 IGF1 传入大脑的功能后果进行综述,提示了两者之间存在关联。最近,在南欧人群中发现了与 AD 风险增加和 IGF1 循环水平升高相关的 rs972936 多态性。为了评估 IGF1 多态性在中国汉族人群中发生迟发性 AD(LOAD)的风险,我们在汉族人群中进行了一项独立的病例对照关联研究(794 例 LOAD 病例和 796 例对照)。LOAD 病例和对照组之间在基因型和等位基因频率方面存在显著差异(基因型 P = 0.006,等位基因 P = 0.047)。与 C 等位基因相比,rs972936 的 T 等位基因发生 LOAD 的风险增加了 1.16 倍,这与白种人群的报告结果不同。在 APOEɛ4 携带状态分层后,rs972936 多态性仅在非 APOEɛ4 等位基因携带者中与 LOAD 显著相关(基因型 P = 0.002,等位基因 P = 0.039)。多变量 logistic 回归分析还表明,在调整年龄、性别和 APOEɛ4 携带状态后,SNP rs972936 与 LOAD 之间在隐性和加性模型中存在这种正关联。这些结果表明,IGF1 多态性可能在改变汉族人群中 LOAD 的遗传易感性方面发挥作用。

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