title: Genetic analysis of lysosomal alpha-galactosidase A gene in sporadic Parkinson's disease.
abstract: Parkinson's disease (PD) is a progressive neurodegenerative disease. Majority of PD cases are sporadic, resulting from interaction of genetic and environmental factors. Accumulating evidence indicates that autophagy, which delivers alpha-synuclein to lysosomes for degradation, is involved in the PD pathogenesis. Some lysosomal hydrolases, such as glucocerebrosidase gene and ATP13A2, a lysosomal ATPase gene, have been implicated in PD. We have previously screened the activities of a group of lysosomal hydrolases in sporadic PD patients and found that alpha-galactosidase A (GLA) activities are significantly decreased. In this study, we analyzed GLA gene in sporadic PD patients by sequencing its promoter and exon regions. One single-nucleotide polymorphism (SNP) in the promoter region, rs3027580 (NG_007119.1:g.4292G>C), and two SNPs in the GLA 5'-untranslated region, rs2071225 (NM_000169.2:c.-10C>T) and rs3027585 (NM_000169.2:c.-12G>A), were identified with similar frequencies in sporadic PD patients and healthy controls. A novel variant (NG_007119.1:g.4488C>G) within the promoter region, at the -573 site upstream of the translation start codon (ATG), was found in one male PD patient, but not in female PD patients or healthy controls. Our data suggest that the sequence variant may affect GLA gene expression by altering transcription factor binding sites, contributing to the pathogenesis of sporadic PD.
authors.affiliation: Division of Cardiac Surgery, Jining Medical College Affiliated Hospital, Jining Medical College, 79 Guhuai Road, Jining, Shandong 272029, China.
authors.forename: Guanghua
authors.initials: G
authors.lastname: Wu
authors.forename: Shuchao
authors.initials: S
authors.lastname: Pang
authors.forename: Xungang
authors.initials: X
authors.lastname: Feng
authors.forename: Aimei
authors.initials: A
authors.lastname: Zhang
authors.forename: Jifeng
authors.initials: J
authors.lastname: Li
authors.forename: Kejin
authors.initials: K
authors.lastname: Gu
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
authors.forename: Haixin
authors.initials: H
authors.lastname: Dong
authors.forename: Bo
authors.initials: B
authors.lastname: Yan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008247:Lysosomes / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D000519:alpha-Galactosidase / Q000235:genetics*
chemical_list: D000519:alpha-Galactosidase