Department of Psychiatry, Faculty of Medicine, The Chinese University of Hong Kong, China.
Department of Chemical Pathology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
Curr Alzheimer Res. 2020;17(13):1232-1237. doi: 10.2174/1567205018666210208163946.
Pin1 is a propyl cis-trans isomerase and it has been associated with age-atonset of Alzheimer's disease (AD) and other pathological characteristics of AD. DNA methylation is one of the gene regulation mechanisms and it might affect the gene expression.
This study was aimed to examine the correlation between DNA methylation and gene expression of Pin1 and its effect on the risk of AD in a Chinese population.
80 AD patients and 180 normal controls were recruited in this study and their cognitive functions were assessed. Pin1 gene expression and methylation were quantified by real-time RT-PCR and Melting Curve Analysis-Methylation assay (MCA-Meth), respectively.
Our finding revealed a positive correlation between methylation and gene expression of Pin1 (p=0.001) and increased Pin1 methylation was predisposed to the risk of AD (p<0.001). CG genotype of Pin1 SNP rs2287839 was associated with higher gene expression of Pin1 (p=0.036) and the effect was only prominent in normal controls as AD patients were already methylated at Pin1 promoter. Furthermore, methylation of Pin1 was associated with better performance in cognition (p=0.018).
Our result further supported the involvement of Pin1 in AD and the increased level of Pin1 might be a protective factor for AD.
Pin1 是一种脯氨酸顺反异构酶，它与阿尔茨海默病（AD）的发病年龄和 AD 的其他病理特征有关。DNA 甲基化是一种基因调控机制，它可能影响基因表达。
本研究旨在探讨中国人群中 Pin1 的 DNA 甲基化与基因表达的相关性及其对 AD 发病风险的影响。
本研究纳入 80 例 AD 患者和 180 例正常对照者，评估其认知功能。采用实时 RT-PCR 和熔解曲线分析-甲基化分析（MCA-Meth）分别定量 Pin1 基因表达和甲基化。
我们的研究结果显示，Pin1 的甲基化与基因表达呈正相关（p=0.001），Pin1 甲基化增加易患 AD（p<0.001）。Pin1 SNP rs2287839 的 CG 基因型与 Pin1 基因表达增加相关（p=0.036），这种影响仅在正常对照组中显著，因为 AD 患者的 Pin1 启动子已经甲基化。此外，Pin1 的甲基化与认知表现较好相关（p=0.018）。
我们的研究结果进一步支持了 Pin1 参与 AD 的发生，Pin1 水平的升高可能是 AD 的保护因素。
