Determining the Effect of the HNMT, STK39, and NMD3 Polymorphisms on the Incidence of Parkinson's Disease, Amyotrophic Lateral Sclerosis, and Multiple System Atrophy in Chinese Populations
Determining the Effect of the HNMT, STK39, and NMD3 Polymorphisms on the Incidence of Parkinson's Disease, Amyotrophic Lateral Sclerosis, and Multiple System Atrophy in Chinese Populations
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确定 HNMT、STK39 和 NMD3 多态性对中国人群帕金森病、肌萎缩侧索硬化症和多系统萎缩症发病率的影响
DOI：
10.1007/s12031-018-1048-8
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发表时间：
2018-04-01
影响因子：
3.1
通讯作者：
Shang, Hui-Fang
中科院分区：
文献类型：
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作者：
Chen, Yongping;Cao, Bei;Shang, Hui-Fang
全基因组关联研究的大规模荟萃分析已经确定了几个与散发性帕金森病（PD）相关的基因位点。然而，一些重要位点，如HNMT基因的Thr105Ile、STK39基因的rs2390669以及NMD3基因的rs34016896，在中国人群中的作用尚未明确。越来越多的证据表明，不同的神经退行性疾病具有一些共同的临床病理特征。因此，我们进行了一项大样本研究，以调查这些变异与中国人群中的帕金森病、多系统萎缩（MSA）和肌萎缩侧索硬化（ALS）之间的关联。本研究共检查了2417名患者，包括1237名帕金森病患者、850名散发性肌萎缩侧索硬化（SALS）患者和330名多系统萎缩患者，以及836名健康对照（HCs）。所有患者均使用Sequenom iPLEX分析法对单核苷酸多态性（SNPs）进行基因分型。在所研究的三种神经退行性疾病和三个候选变异之间，基因型和等位基因频率分布没有发现显著差异。在亚组分析中，与以震颤为首发症状的帕金森病患者和健康对照相比，以强直/运动迟缓为首发症状的帕金森病患者中NMD3基因rs34016896的次要等位基因频率显著较低。此外，携带rs34016896次要等位基因的女性患者患多系统萎缩的风险增加（比值比为1.25，95%置信区间[1.09 - 1.43]），并且在HNMT基因Thr105Ile等位基因上携带Ile105多态性的肌萎缩侧索硬化患者表现出症状发作延迟3.010 ± 1.629年的趋势。我们的研究结果表明，NMD3基因中rs34016896等位基因的存在可能有助于突触核蛋白病的发展，并且HNMT基因中的Thr105Ile等位基因可能是治疗肌萎缩侧索硬化的一个重要治疗靶点。
Large-scale meta-analyses of genome-wide association studies have identified several loci linked to sporadic Parkinson's disease (PD). However, the roles of some important loci, such as HNMT Thr105Ile, STK39 rs2390669, and NMD3 rs34016896, have not been clarified in Chinese populations. Accumulating evidence indicates that some common clinicopathological characteristics are shared by different neurodegenerative diseases. Consequently, we conducted a large sample study to investigate associations between these variants and PD, multiple system atrophy (MSA), and amyotrophic lateral sclerosis (ALS) in Chinese populations. A total of 2417 patients, including 1237 PD, 850 SALS, and 330 MSA patients, along with 836 healthy controls (HCs) were examined in this study. All patients were genotyped for SNPs using the Sequenom iPLEX assay. No significant differences were found in the genotype and allele frequency distributions between the three neurodegenerative diseases and three candidate variants investigated. In subgroup analysis, compared with PD patients with initial symptom of tremor and HCs, the minor allele frequency of NMD3 rs34016896 in PD patients with initial symptoms of rigidity/bradykinesia was significantly lower. In addition, female patients carrying the rs34016896 minor allele had an increased risk of developing MSA (OR 1.25, 95% CI [1.09-1.43]), and ALS patients carrying the Ile105 polymorphism on the Thr105Ile allele in the HNMT gene exhibited a trend toward a delay in symptom onset of 3.010 +/- 1.629 years. Our results indicate that the presence of the rs34016896 allele in the NMD3 gene may contribute to the development of synucleinopathies and that the Thr105Ile allele in the HNMT gene could potentially be an important therapeutic target for the treatment of ALS.