title: Novel and functional ATG12 gene variants in sporadic Parkinson's disease.
abstract: Parkinson's disease (PD) is a common and progressive neurodegenerative disease, including familial and sporadic cases. To date, genetic causes for sporadic PD, majority of PD cases, remain largely unknown. Accumulating evidence indicates that dysfunctional autophagy, a highly conserved cellular process, is involved in the PD pathogenesis. We speculated that changed expression levels of autophagy-related genes (ATG) may contribute to PD development. Previously, we have genetically analyzed ATG5 and ATG7 genes in sporadic PD patients and identified several functional DNA sequence variants (DSVs). In groups of sporadic PD patients and ethic-matched healthy controls in this study, we further genetically and functionally analyzed the promoter of ATG12, a critical gene for autophagososme formation. The results showed that three DNA sequence variants (DSVs), g.115842507G>T,g.115842394C>T and g.115841817_18del, were identified three PD patients, which significantly altered transcriptional activity of ATG12 gene promoter, probably due to abolishing or creating binding sites for transcription factors. The transcriptional activity of ATG12 gene promoter was not significantly affected by other two DSVs identified in PD patients, g.115842640A>C and g.115842242G>C, which may not alter binding sites for transcription factors. Therefore, these three functional DSVs identified in PD patient may change ATG12 protein levels, contributing to PD development as a risk factor by interfering with autophagy as well as non-autophagy functions.
authors.affiliation: Division of Transcranial Doppler Ultrasound, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong 272029, China.
authors.forename: Yuequn
authors.initials: Y
authors.lastname: Li
authors.affiliation: Shandong Provincial Sino-US Cooperation Center for Translational Medicine, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong, 272029, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
authors.affiliation: Shandong Provincial Sino-US Cooperation Center for Translational Medicine, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong, 272029, China.
authors.forename: Shuchao
authors.initials: S
authors.lastname: Pang
authors.affiliation: Shandong Provincial Sino-US Cooperation Center for Translational Medicine, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong, 272029, China.
authors.forename: Haihua
authors.initials: H
authors.lastname: Wang
authors.affiliation: Division of Neurology, Affiliated Hospital of Jining Medical University, Jining Medical, University, Jining, Shandong 272029, China.
authors.forename: Aimei
authors.initials: A
authors.lastname: Zhang
authors.affiliation: Shandong Provincial Sino-US Cooperation Center for Translational Medicine, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong, 272029, China; Department of Anatomy and Regenerative Biology, The George Washington University, 2300, Eye Street, NW, Washington, DC 20037, USA. Electronic address: rghawley@gwu.edu.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Hawley
authors.affiliation: Shandong Provincial Sino-US Cooperation Center for Translational Medicine, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong, 272029, China; Department of Anatomy and Regenerative Biology, The George Washington University, 2300, Eye Street, NW, Washington, DC 20037, USA. Electronic address: yanbo@mail.jnmc.edu.cn.
authors.forename: Bo
authors.initials: B
authors.lastname: Yan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001343:Autophagy / Q000235:genetics*; D000071192:Autophagy-Related Protein 12 / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*
chemical_list: C466624:ATG12 protein, human; D000071192:Autophagy-Related Protein 12
keywords: ATG12; Autophagy; DNA sequence variant; Parkinson's disease; Promoter