Wang Lixia, Huang Jian, Pang Shuchao, Qin Xianyun, Qi Ziyou, Hawley Robert G, Yan Bo
Center for Reproductive Medicine, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong 272029, China.
Shandong Provincial Sino-US Cooperation Center for Translational Medicine, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong, 272029, China.
Neurosci Lett. 2017 Apr 12;646:30-35. doi: 10.1016/j.neulet.2017.03.007. Epub 2017 Mar 6.
Parkinson's disease (PD) is a common and progressive neurodegenerative disease in which the majority of cases arise sporadically. Sporadic PD is caused by the interactions of genetic and environmental factors. To date, genetic causes for sporadic PD remain largely unknown. Autophagy, a highly conserved cellular process, has been implicated in PD pathogenesis. We speculated that genetic variants in autophagy-related genes (ATG) that regulate gene expression may contribute to PD development. In our previous studies, we have identified several functional DNA sequence variants (DSVs) in the ATG5, ATG7 and LC3 genes in sporadic PD patients. In this study, we further genetically and functionally analyzed the promoter of the ATG16L1 gene, a critical gene for autophagosome formation, in groups of sporadic PD patients and ethnic-matched healthy controls. One novel heterozygous DSV, 233251432C>T, was found in one PD patient. Functionally, this DSV did not affect the transcriptional activity of the ATG16L1 gene promoter in human dopaminergic SH-SY5Y cells. Two heterozygous DSVs including one SNP, 233251286G>A (rs539735288) and 233251582C>T, were found only in controls. In addition, five other SNPs were found in both PD patients and controls. Taken together, the data suggested that genetic variants within the ATG16L1 gene promoter were not a risk factor for sporadic PD development.
帕金森病（PD）是一种常见的进行性神经退行性疾病，大多数病例为散发性。散发性PD由遗传和环境因素相互作用引起。迄今为止，散发性PD的遗传原因仍 largely未知。自噬是一种高度保守的细胞过程，与PD发病机制有关。我们推测，调节基因表达的自噬相关基因（ATG）中的遗传变异可能导致PD的发展。在我们之前的研究中，我们在散发性PD患者的ATG5、ATG7和LC3基因中鉴定了几个功能性DNA序列变异（DSV）。在本研究中，我们进一步对自噬体形成的关键基因ATG16L1基因的启动子进行了遗传和功能分析，研究对象为散发性PD患者组和种族匹配的健康对照。在一名PD患者中发现了一个新的杂合DSV，233251432C>T。在功能上，该DSV不影响人多巴胺能SH-SY5Y细胞中ATG16L1基因启动子的转录活性。仅在对照组中发现了两个杂合DSV，包括一个SNP，233251286G>A（rs539735288）和233251582C>T。此外，在PD患者和对照组中均发现了其他五个SNP。综上所述，数据表明ATG16L1基因启动子内的遗传变异不是散发性PD发展的危险因素。
