Frequency of Parkinson's Disease Genes and Role of PARK2 in Amyotrophic Lateral Sclerosis: An NGS Study.
Frequency of Parkinson's Disease Genes and Role of PARK2 in Amyotrophic Lateral Sclerosis: An NGS Study.
复制标题
帕金森病基因的频率和PARK2在肌萎缩侧索硬化症中的作用：NGS研究
作者：
肌萎缩侧索硬化症（ALS）和阿尔茨海默病（AD）患者的路易体病的患病率高于一般人群。此外，在约30%的ALS患者中发现了帕金森病特征。我们的目的是探索ALS患者与AD和健康对照（HC）相比，帕金森病（PD）致病基因的频率。我们通过分析SNCA、LRRK2、PINK1、PARK2、PARK7、SYNJ1、CHCHD2、PLA2G6、GCH 1、ATP 13 A2、DNAJC 6和FBXO基因，使用下一代测序多基因板。同时对PD的危险因素GBA基因进行了分析。总共调查了130名ALS和100名AD患者。PD相关基因在ALS、AD和HC患者中的改变率分别为26.2%、20%和19.2%。与AD和HC相比，常染色体隐性遗传基因在ALS中的参与程度更高（p = 0.021）。PARK2变异在ALS中比在AD和HC中更常见，尽管不显著。然而，p.Arg402Cys变体在ALS中比在HC中增加（p = 0.025）。这一发现与目前的文献一致，因为在ALS动物模型和患者中发现parkin水平降低。我们的研究结果证实了PD相关基因在ALS发病机制中作为风险修饰因子的可能作用。
Amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease (AD) patients show a higher prevalence of Lewy body disease than the general population. Additionally, parkinsonian features were found in about 30% of ALS patients. We aimed to explore the frequency of Parkinson’s disease (PD)-causative genes in ALS patients, compared to AD and healthy controls (HCs). We used next-generation sequencing multigene panels by analyzing SNCA, LRRK2, PINK1, PARK2, PARK7, SYNJ1, CHCHD2, PLA2G6, GCH1, ATP13A2, DNAJC6 and FBXO genes. GBA gene, a risk factor for PD, was also analyzed. In total, 130 ALS and 100 AD patients were investigated. PD-related genes were found to be altered in 26.2% of ALS, 20% of AD patients and 19.2% of HCs. Autosomal recessive genes were significantly more involved in ALS as compared to AD and HCs (p = 0.021). PARK2 variants were more frequent in ALS than in AD and HCs, although not significantly. However, the p.Arg402Cys variant was increased in ALS than in HCs (p = 0.025). This finding is consistent with current literature, as parkin levels were found to be decreased in ALS animal models and patients. Our results confirm the possible role of PD-related genes as risk modifier in ALS pathogenesis.
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DOI：
10.1016/j.prdoa.2019.08.006
发表时间：
2019-01-01
期刊：
Clinical parkinsonism & related disorders
影响因子：
--
作者：
Kim, Hojoong M;Nazor, Carter;Cholerton, Brenna
通讯作者：
Cholerton, Brenna
影响因子：
3.6
作者：
Ho, Dong Hwan;Kim, Hyejung;Seol, Wongi
通讯作者：
Seol, Wongi
影响因子：
9.9
作者：
Chio, Adriano;Moglia, Cristina;Calvo, Andrea
通讯作者：
Calvo, Andrea
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
影响因子：
3.7
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
通讯作者：
Shang HF
影响因子：
6.2
作者：
Caesar, Mareike;Felk, Sandra;Gillardon, Frank
通讯作者：
Gillardon, Frank