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探索 16 个候选基因,确定 IDE 与汉族人群阿尔茨海默病的关联性。

Exploration of 16 candidate genes identifies the association of IDE with Alzheimer's disease in Han Chinese.

机构信息

Department of Neurology, Xuan Wu Hospital of the Capital Medical University, Beijing, China.

出版信息

Neurobiol Aging. 2012 May;33(5):1014.e1-9. doi: 10.1016/j.neurobiolaging.2010.08.004. Epub 2010 Sep 28.

Abstract

Alzheimer's disease (AD) has a complex pattern of inheritance and many genes have recently been reported to contribute to the disease susceptibility. We selected 106 SNPs within 16 candidate genes and performed a multistage association study using 4 sample sets consisting of 731 AD patients and 738 control subjects to identify genetic factors for AD in Han Chinese. A single nucleotide polymorphism (SNP) in the insulin degrading enzyme gene (IDE), rs3781239, showed a significant association with AD. The C allele increased the risk of AD 1.72-fold than the G allele (odds ratio [OR] = 1.72, 95% confidence interval [CI] = 1.17-2.53, p = 0.006) and CC carriers had a 4.89-fold higher risk for AD than that of the carriers with CG and GG genotypes (odds ratio = 4.89, 95% CI = 1.85-12.91, p = 0.001). Moreover, the CC genotype was significantly associated with earlier age at onset (p = 0.001, hazard ratio [HR] = 2.09, 95% CI = 1.38-3.18). Our data suggest that the polymorphism of IDE is associated with susceptibility to Alzheimer's disease in Han Chinese.

摘要

阿尔茨海默病(AD)具有复杂的遗传模式,许多基因最近被报道与疾病易感性有关。我们选择了 16 个候选基因中的 106 个 SNP,并使用由 731 名 AD 患者和 738 名对照组成的 4 个样本集进行了多阶段关联研究,以确定汉族人群中 AD 的遗传因素。胰岛素降解酶基因(IDE)中的一个单核苷酸多态性(SNP)rs3781239 与 AD 显著相关。C 等位基因使 AD 的风险增加 1.72 倍,而 G 等位基因(比值比[OR] = 1.72,95%置信区间[CI] = 1.17-2.53,p = 0.006),CC 携带者比 CG 和 GG 基因型携带者患 AD 的风险高 4.89 倍(比值比= 4.89,95%CI = 1.85-12.91,p = 0.001)。此外,CC 基因型与发病年龄较早显著相关(p = 0.001,风险比[HR] = 2.09,95%CI = 1.38-3.18)。我们的数据表明,IDE 的多态性与汉族人群中阿尔茨海默病的易感性有关。

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