Genetic Variants of SNCA Are Associated with Susceptibility to Parkinson's Disease but Not Amyotrophic Lateral Sclerosis or Multiple System Atrophy in a Chinese Population.
Genetic Variants of SNCA Are Associated with Susceptibility to Parkinson's Disease but Not Amyotrophic Lateral Sclerosis or Multiple System Atrophy in a Chinese Population.
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SNCA 的遗传变异与中国人群帕金森病的易感性相关，但与肌萎缩侧索硬化症或多系统萎缩症无关
DOI：
10.1371/journal.pone.0133776
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Shang HF
中科院分区：
文献类型：
--
作者：
Chen Y;Wei QQ;Ou R;Cao B;Chen X;Zhao B;Guo X;Yang Y;Chen K;Wu Y;Song W;Shang HF
本研究对高加索人群中与帕金森病(PD)密切相关的α-突触核蛋白(SNCA)基因rs3775444、rs3822086和rs11931074进行了检测，以探讨其在不同种族背景中的作用。根据帕金森病、肌萎缩侧索硬化症(ALS)和多系统萎缩(MSA)这三种神经退行性疾病的临床表现和病理特征的重叠，还研究了这三种基因多态性在中国人群中的可能关联。共有1276名帕金森病患者、885名散发性肌萎缩侧索硬化症(SALS)、364名MSA患者和846名健康对照(HCS)纳入研究。使用Sequenom IPLEX分析技术对所有受试者进行三个基因多态的基因分型。SNCA基因rs3822086(C)和rs11931074(G)的基因型分布(p=5.99E-06和p=4.98E-06)和次要等位基因频率(MAF)(分别为p=2.16E-06和p=2.15E-06)在PD和HCS之间存在显著差异。而SNCA基因rs3775444(T)的基因型分布和MAF在PD组和HCS组之间无明显差异。整合了三个SNP的单倍型进一步加强了与帕金森病的关联(最佳单倍型，p=9.62E-005)。SALS与HCS、MSA与HCS、PD亚组与SALS亚组间的SNPs基因分布及MAF差异均无统计学意义。额叶功能障碍组SNCArs3775444(T)的MAF显著高于无额叶功能障碍组(P=0.0002，OR2.53，95%CI：1.55~4.15)。结果提示，SNCA的rs3822086(C)等位基因和rs11931074(G)等位基因降低了中国人患PD的风险，SNCA的rs11931074可能影响MSA的额叶功能障碍。然而，这些SNCA基因多态性不太可能是SALS或MSA的常见原因。
The polymorphisms of α-synuclein (SNCA), rs3775444, rs3822086 and rs11931074 that are strongly associated with Parkinson’s disease (PD) in Caucasian populations, were examined in this study to elucidate the role of polymorphisms in different ethnic backgrounds. The possible associations of these three polymorphisms were also investigated in PD, amyotrophic lateral sclerosis (ALS), and multiple system atrophy (MSA) in a Chinese population based on the overlapping of clinical manifestations and pathological characteristics of these three neurodegenerative diseases. A total of 1276 PD, 885 sporadic ALS (SALS), 364 MSA patients, and 846 healthy controls (HCs) were included. All subjects were genotyped for the three polymorphisms using Sequenom iPLEX Assay technology. Significant differences in the genotype distributions (p = 5.99E-06 and p = 4.98E-06, respectively) and the minor allele frequency (MAF) (p = 2.16E-06 and p = 2.15E-06, respectively) of SNCA rs3822086 (C) and rs11931074 (G) were observed between PD and HCs. However, no differences were found in the genotype distributions and MAF of SNCA rs3775444 (T) between PD and HCs. Haplotype that incorporated the three SNPs further strengthened the association with PD (best haplotype, p = 9.62E-005). No significant differences in the genotype distributions and MAF of the SNPs were found between SALS and HCs, MSA and HCs, and subgroups of PD and SALS. However, the MAF of SNCA rs3775444 (T) was significantly higher in MSA patients with frontal lobe dysfunction than MSA patients without dysfunction (p = 0.0002, OR 2.53, 95%CI: 1.55-4.15). Our results suggest that the rs3822086 (C) allele and rs11931074 (G) allele in SNCA decrease the risk for PD, and SNCA rs11931074 may affect frontal lobe dysfunction of MSA in the Chinese population. However, these SNCA polymorphisms are not likely a common cause of SALS or MSA.