在中国汉族人群中,ACMSD/TMEM163、GPNMB 和 BCKDK/STX1B 三个候选基因变异与散发性帕金森病的关联。

Association of three candidate genetic variants in ACMSD/TMEM163, GPNMB and BCKDK /STX1B with sporadic Parkinson's disease in Han Chinese.

机构信息

Department of Neurology, West China Hospital, Sichuan University, Sichuan, China.

Department of Neurology, West China Hospital, Sichuan University, Sichuan, China.

出版信息

Neurosci Lett. 2019 Jun 11;703:45-48. doi: 10.1016/j.neulet.2019.03.019. Epub 2019 Mar 14.

Abstract

Large-scale meta-analyses of genome-wide association studies have identified that polymorphisms ACMSD/TMEM163 rs6430538, GPNMB rs199347 and BCKDK /STX1B rs14235 to be the risk loci for Parkinson's disease (PD) in a Caucasian population. However, the role of these three polymorphisms in a Han Chinese population from mainland China still remains to be clarified. We conducted a large sample study to examine genetic associations of rs6430538, rs199347 and rs14235 with PD in a Han Chinese population of 989 sporadic PD patients and 1058 healthy controls. All subjects were genotyped for these loci using the Sequenom iPLEX Assay. In addition, we conducted further stratified analysis according to age at onset and compared the clinical characteristics between minor allele carriers and non-carriers for each locus. However, no significant differences were found in genotype and allele frequency distribution between PD patients and controls for the three loci, even after being stratified by age at onset. Moreover, we demonstrated that minor allele carriers cannot be distinguished from non-carriers based on their clinical features. Our study is the first to demonstrate that ACMSD/TMEM163 rs6430538, GPNMB rs199347 and BCKDK /STX1B rs14235 do not confer a significant risk for sporadic PD in mainland China. Therefore, more replication studies in additional Chinese population and other cohorts and functional studies are warranted to further clarify the role of the three loci in PD susceptibility.

摘要

大规模的全基因组关联研究荟萃分析已经确定,ACMSD/TMEM163 基因上的 rs6430538、GPNMB 基因上的 rs199347 和 BCKDK/STX1B 基因上的 rs14235 多态性是高加索人群中帕金森病(PD)的风险位点。然而,这三个多态性在中国汉族人群中的作用仍有待阐明。我们进行了一项大样本研究,以检验 rs6430538、rs199347 和 rs14235 与汉族散发性 PD 患者(989 例)和 1058 例健康对照者的遗传关联。所有受试者均使用Sequenom iPLEX 分析进行了这些基因座的基因分型。此外,我们还根据发病年龄进行了进一步的分层分析,并比较了每个基因座的小等位基因携带者和非携带者的临床特征。然而,三个基因座的基因型和等位基因频率分布在 PD 患者和对照组之间没有显著差异,即使在按发病年龄分层后也是如此。此外,我们证明小等位基因携带者不能根据其临床特征与非携带者区分开来。本研究首次表明,ACMSD/TMEM163 基因上的 rs6430538、GPNMB 基因上的 rs199347 和 BCKDK/STX1B 基因上的 rs14235 在中国大陆的散发性 PD 中不能显著增加发病风险。因此,需要在其他中国人群和其他队列中进行更多的复制研究,并进行功能研究,以进一步阐明这三个基因座在 PD 易感性中的作用。

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