The LRRK2 R1628P Variant Plays a Protective Role in Han Chinese Population with Alzheimer's Disease
The LRRK2 R1628P Variant Plays a Protective Role in Han Chinese Population with Alzheimer's Disease
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DOI：
10.1111/cns.12062
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发表时间：
2013-04-01
影响因子：
5.5
通讯作者：
Wu, Zhi-Ying
中科院分区：
文献类型：
--
作者：
Li, Hong-Lei;Lu, Shen-Ji;Wu, Zhi-Ying
阿尔茨海默病（Alzheimer's disease，AD）和帕金森病（Parkinson's disease，PD）是最常见的两种神经退行性疾病。据报道，富含亮氨酸重复序列激酶2（LRRK 2）内的突变与PD有关，LRRK 2的位置位于散发性AD（SAD）的连锁峰内。本研究的目的是探讨两个亚洲特异性LRRK 2变异体R1628 P和G2385 R与中国汉族SAD的关联。方法采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术对390例SAD患者和545例年龄、性别匹配的健康对照者进行R1628 P和G2385 R基因分型。结果对照组R1628 P C等位基因频率（1.7%）是SAD组（0.5%）的3倍多（OR 0.264; 95%CI为0.0880.792，P=0.018）。按存在一个或两个载脂蛋白E等位基因分层后，保护作用变得更强（OR 0.028; 95%CI，0.0030.303，P=0.003; OR 0.104; 95%CI，0.0130.818，P=0.031）。而G2385 R变异体则无差异。结论LRRK 2基因R1628 P变异对SAD患者具有保护作用，且这种保护作用与APOE基因型存在交互作用。
Aims Alzheimer's disease (AD) and Parkinson's disease (PD) are the most prevalent neurodegenerative disorders that may share some overlapping etiologies. Mutations within leucine-rich repeat kinase 2 (LRRK2) have been reported to be responsible for PD, and the location of LRRK2 is within a linkage peak for sporadic AD (SAD). The aim of this study was to investigate two Asian-specific LRRK2 variants, R1628P and G2385R, with the association of Han Chinese SAD. Methods Genotyping of R1628P and G2385R was performed by PCR-restriction fragment length polymorphism (RFLP) analysis in 390 patients with SAD and 545 unrelated age- and sex-matched healthy controls. Results The frequency of the C allele within R1628P was more than three times higher in control group (1.7%) than in patients with SAD (0.5%) (OR 0.264; 95% CI, 0.0880.792, P=0.018). After stratification by the presence of one or two apolipoprotein E epsilon 4 alleles, the protective effect becomes stronger (epsilon 44: OR 0.028; 95% CI, 0.0030.303, P=0.003; epsilon 4: OR 0.104; 95% CI, 0.0130.818, P=0.031). However, no difference was found in G2385R variant. Conclusion Our study suggested that R1628P variant within LRRK2 plays a protective role in Han Chinese population with SAD and such effect has an interaction with the APOE genotype.