Alzheimer's disease susceptibility genes modify the risk of Parkinson disease and Parkinson's disease-associated cognitive impairment
Alzheimer's disease susceptibility genes modify the risk of Parkinson disease and Parkinson's disease-associated cognitive impairment
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阿尔茨海默病易感基因改变帕金森病和帕金森病相关认知障碍的风险
DOI：
10.1016/j.neulet.2018.04.042
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发表时间：
2018
影响因子：
2.5
通讯作者：
Guo Ji feng
中科院分区：
文献类型：
--
作者：
Fang Lu;Tang Bei sha;Fan Kuan;Wan Chang min;Yan Xin xiang;Guo Ji feng
帕金森病 (PD) 和 PD-认知障碍 (CI) 的致病机制仍然难以捉摸。它与阿尔茨海默病 (AD) 危险因素的潜在联系尚不清楚。在这项研究中，我们分析了中国 450 例 PD 病例和 449 例对照队列中 12 个基因的 16 个 CE 相关单核苷酸多态性 (SNP)。在我们进行 CI 临床评估的 298 例患者中，113 例没有出现 CI 体征（PD-NC），86 例有轻度认知障碍（PD-MCI），99 例有痴呆（PD-D）。我们发现 APOEε4 等位基因与 PD-D 的较高风险相关。基因-基因相互作用分析显示，三个显着的基因-基因相互作用，包括BDNF和CLU、APOE和CR1、DYRK1A和CD2AP，会增加PD的风险。由于这些 SNP 是已知的 AD 遗传风险因素，因此本研究中显示的它们对 PD 和 PD-D 的贡献表明，PD/PD-D 和 AD 可能通过基因-基因相互作用在其发病机制中共享趋同途径。
The pathogenic mechanism underlying Parkinson’s disease (PD) and PD- Cognitive impairment (CI) remains elusive. Its potential link to the risk factors in Alzheimer’s disease (AD) is unclear. In this study, we analyzed 16 CE-associated single nucleotide polymorphisms (SNPs) in twelve genes in a Chinese cohort of 450 PD cases and 449 controls. Among our 298 cases clinically evaluated for CI, 113 cases did not show CI signs (PD-NC), 86 cases had mildly cognitive impairment (PD-MCI) and 99 cases had dementia (PD-D). We found that theAPOEε4 allele is associated with a higher risk for PD-D. Gene-gene interaction analysis revealed that three significant gene–gene interactions, includingBDNFandCLU,APOEandCR1, andDYRK1AandCD2APincrease the risk for PD. Because these SNPs are known genetic risk factors for AD, their contribution to PD and PD-D shown in this study suggests that PD/PD-D and AD may share convergent pathways in their pathogenesis through gene–gene interactions.