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中国帕金森病患者纤溶酶原激活物抑制剂-1基因多态性与易感性的关系。

Association between plasminogen activator inhibitor-1 gene polymorphisms and susceptibility to Parkinson's disease in Chinese patients.

作者信息

Xu Qi, Lai Qilun, Wang Junjun, Zhuang Liying, Cheng Lin, Mo Yejia, Liu Lu, Zhao Zexian, Zhang Ying, Weng Shiting, Qiao Song

机构信息

Department of Radiology, Zhejiang Hospital, Hangzhou, 310000, China.

Department of Neurology, Zhejiang Hospital, Hangzhou, 310000, China.

出版信息

Acta Neurol Belg. 2022 Dec;122(6):1557-1566. doi: 10.1007/s13760-021-01843-7. Epub 2021 Nov 29.

Abstract

PURPOSE

Parkinson's disease (PD) is a neurodegenerative disease that usually leads to memory impairment, cognitive decline and dementia. Previous studies have reported that plasminogen activator inhibitor-1 (PAI-1) gene polymorphisms play important roles in cardiovascular diseases, obesity, inflammation and other diseases. However, the role of PAI-1 in the diagnosis of Parkinson's disease has not been reported so far.

METHODS

This study was a case-control study. This study included 131 PD patients and 97 healthy volunteers. polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to analyze the polymorphic loci of five different regions in PAI-1 gene (rs2227631, rs1799889, rs6092, rs2227694 and rs7242). 60 PD patients and 60 healthy volunteers were selected to detect the plasma PAI-1 concentration. The allele and genotype frequencies of SNPs were assessed using the SHEsis program.

RESULTS

We found that GG genotype frequency and G allele frequency of rs2227631 was significantly higher in the PD patients. Statistically significant difference for rs1799889 could be observed in overdominant model. In subgroup analysis, a significant difference in genotype frequency distribution and allele frequency was found for rs2227631 and rs1799889 between early-onset PD group and the control group. For cognitive dysfunction, the subcomponent showed that GG genotype frequency and G allele frequency of rs2227631 was significantly higher in normal cognition group. The codominant model of rs1799889 was significantly different between the cognitive impairment group and the control group. In addition, the expression of PAI-1 in plasma of PD patients was significantly higher than that of controls, and further analysis showed that the expression of PAI-1 in patients with cognitive impairment was significantly higher than that in patients with cognitive normal.

CONCLUSION

Our results indicate that the PAI-1 gene rs2227631 and rs1799889 polymorphisms were significantly associated with PD susceptibility in the Chinese Han population. PAI-1 has the potential to become a new therapeutic target and diagnostic marker.

摘要

目的

帕金森病(PD)是一种神经退行性疾病,通常会导致记忆障碍、认知衰退和痴呆。先前的研究报道纤溶酶原激活物抑制剂-1(PAI-1)基因多态性在心血管疾病、肥胖、炎症及其他疾病中发挥重要作用。然而,PAI-1在帕金森病诊断中的作用迄今尚未见报道。

方法

本研究为病例对照研究。研究纳入131例PD患者和97名健康志愿者。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析PAI-1基因五个不同区域(rs2227631、rs1799889、rs6092、rs2227694和rs7242)的多态性位点。选取60例PD患者和60名健康志愿者检测血浆PAI-1浓度。使用SHEsis软件评估单核苷酸多态性(SNP)的等位基因和基因型频率。

结果

我们发现rs2227631的GG基因型频率和G等位基因频率在PD患者中显著更高。在超显性模型中可观察到rs1799889有统计学显著差异。亚组分析显示,早发型PD组与对照组之间rs2227631和rs1799889的基因型频率分布和等位基因频率存在显著差异。对于认知功能障碍,亚组分析表明rs2227631的GG基因型频率和G等位基因频率在正常认知组中显著更高。rs1799889的共显性模型在认知障碍组与对照组之间有显著差异。此外,PD患者血浆中PAI-1的表达显著高于对照组,进一步分析表明认知障碍患者中PAI-1的表达显著高于认知正常患者。

结论

我们的结果表明,PAI-1基因rs2227631和rs1799889多态性与中国汉族人群的PD易感性显著相关。PAI-1有潜力成为新的治疗靶点和诊断标志物。

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