title: A novel and functional variant within the ATG5 gene promoter in sporadic Parkinson's disease.
abstract: Parkinson's disease (PD) is one of the most common neurodegenerative diseases. Majority of PD are sporadic, for which genetic causes remain largely unknown. Alpha-synuclein, the main component of Lewy bodies, plays a central role in the PD pathogenesis. Macroautophagy is a highly conserved cellular process that digests dysfunctional macromolecules and damaged organelles. Accumulating evidence indicates that macroautophagy (hereafter referred to as autophagy) is involved in alpha-synuclein degradation. Dysregulation of autophagy has been observed in the brain tissues from PD patients and animal models. We hypothesized that change expression levels of autophagy-related genes (ATG), including ATG5, may contribute to PD. In this study, we genetically and functionally analyzed the ATG5 gene promoter in groups of sporadic PD patients and ethnic-matched healthy controls. A novel heterozygous variant, 106774459T>A, was identified in one female patient, but in none of controls, which significantly enhanced transcriptional activities of the ATG5 gene promoter. Furthermore, ATG5 gene expression level in the PD patient was significantly elevated than that in controls. Four novel heterozygous variants, 106774423C>A, 106774418C>A, 106774382C>A and 106774206G>A, were only found in controls. The variant, 106774464C>T, and SNP-106774030A>G (rs510432) were found in PD patients and controls with similar frequencies. Collectively, the variant identified in PD patient may change ATG5 protein levels and alter autophagy activities, contributing to PD onset as a risk factor.
authors: Shandong Provincial Key Laboratory of Cardiac Disease Diagnosis and Treatment, Jining Medical University Affiliated Hospital, Jining Medical University, Jining, Shandong 272029, China.
authors: Dongfeng
authors: D
authors: Chen
authors: Cuiping
authors: C
authors: Zhu
authors: Xuenan
authors: X
authors: Wang
authors: Xungang
authors: X
authors: Feng
authors: Shuchao
authors: S
authors: Pang
authors: Wenhui
authors: W
authors: Huang
authors: Robert G
authors: RG
authors: Hawley
authors: Bo
authors: B
authors: Yan
mesh_terms: D000368:Aged; D001343:Autophagy; D000071187:Autophagy-Related Protein 5; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006579:Heterozygote; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D010300:Parkinson Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic
chemical_list: C502778:ATG5 protein, human; D000071187:Autophagy-Related Protein 5; D008869:Microtubule-Associated Proteins