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评估中国人群中基因变异与帕金森病之间的关联。

Evaluating the association between variants and Parkinson's disease in the Chinese population.

作者信息

Liu Jiabin, Huang Juanjuan, Zhao Yuwen, Pan Hongxu, Wang Yige, Liu Zhenhua, Xu Qian, Sun Qiying, Tan Jieqiong, Yan Xinxiang, Li Jinchen, Tang Beisha, Guo Jifeng

机构信息

Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China.

National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.

出版信息

Front Neurol. 2023 Feb 24;14:1133449. doi: 10.3389/fneur.2023.1133449. eCollection 2023.

Abstract

INTRODUCTION

Parkinson's disease (PD) is a progressive movement disorder caused by a loss of dopaminergic neurons. Previous studies have highlighted the importance of mitochondria dynamics in the pathogenesis of PD. Dynamin-1-like () is a gene that encodes dynamin-related protein 1 (DRP1), a GTPase essential for proper mitochondria fission. In the present study, we evaluated the relationship between variants and PD in the Chinese population.

METHODS

A total of 3,879 patients with PD and 2,931 healthy controls were recruited and burden genetic analysis combined with high-throughput sequencing was applied.

RESULTS

We identified 23 rare variants in the coding region of , while no difference in variant burden was shown between the cases and controls. We also identified 201 common variants in the coding and flanking regions and found two significant SNPs, namely, rs10844308 and rs143794289 [odds ratio (OR) = 1.220 and 0.718, = 0.025 and 0.036, respectively]. We also performed a meta-analysis to correlate the two SNPs with PD risk. However, none of the common variants was significant using logistic regression.

CONCLUSION

Despite the critical role of DRP1, our study did not support the relationship between variants and PD risk in the Chinese population.

摘要

引言

帕金森病(PD)是一种由多巴胺能神经元丧失引起的进行性运动障碍。先前的研究强调了线粒体动力学在PD发病机制中的重要性。动力蛋白1样()是一个编码动力蛋白相关蛋白1(DRP1)的基因,DRP1是一种对线粒体正常分裂至关重要的GTP酶。在本研究中,我们评估了中国人群中该基因变异与PD之间的关系。

方法

共招募了3879例PD患者和2931例健康对照,并应用了结合高通量测序的负担基因分析。

结果

我们在该基因的编码区鉴定出23个罕见变异,但病例组和对照组之间的变异负担没有差异。我们还在编码区和侧翼区鉴定出201个常见变异,并发现了两个显著的单核苷酸多态性(SNP),即rs10844308和rs143794289[优势比(OR)分别为1.220和0.718,P值分别为0.025和0.036]。我们还进行了荟萃分析,以关联这两个SNP与PD风险。然而,使用逻辑回归分析时,没有一个常见变异具有显著性。

结论

尽管DRP1起着关键作用,但我们的研究不支持中国人群中该基因变异与PD风险之间的关系。

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