RESUMEN
The α-synuclein (SNCA) gene is a pathogenic gene identified in rare familial Parkinson Disease (PD). Recent studies highlight the role of DNA methylation in the pathogenesis of familial and sporadic PD. Hypomethylation in SNCAgene has been associated with increased SNCA gene expression and was observed in post mortem brains of patients with sporadic PD. This study was aimed at evaluating the effect of iron (II) chloride on SH-SY5Y cell models as pertain to cell death caused by oxidative stress, upregulation of SNCA gene expression and reduced SNCA gene methylation. Result obtained from LDH assay showed significant (p<0.05) evidence of cell death in treated cells as compared to the control sample. Analysis for SNCAgene quantification using RT-PCR showed significant increases in fold change. Cells treated with 1000μM of FeCl₂showed the highest fold change of 6.0 while cells treated with 250μM had the lowest fold change of 1.8. In DNA methylation assay using pyrosequencing, cells treated with varying concentrations of FeCl₂showed significant (p<0.05) decrease in DNA methylation. At 250μM, 500μM and 750μM concentrations of FeCl₂, an average mean methylation levels of 1.84%, 1.40% and 1.23% was obtained respectively while cells treated with 1000μM had the lowest average mean methylation level of 1.0%. Thus, the decrease in methylation is linked to the upregulation of the SNCAgene which has been reported to be among the causative factors in the pathogenesis of Parkinson’s disease.
RESUMEN
Objective To explore the association between the single-nucleotide polymorphism (SNP) rs3822086 site of the α-Synuclein(SNCA)gene and Parkinson's disease (PD) of Uygurs versus Hans in Xinjiang,and to compare the distribution difference of this polymorphic site between the Uygurs and Hans.Methods The rs3822086 polymorphism was determined by polymerase chainreaction restriction fragment length polymorphism (PCR-RFLP) in 237 patients with idiopathic Parkinson's disease (IPD,including 92 Uygurs and 145 Hans) and 247 health controls (including 103 Uygurs and 144 Hans).Results In the group aged ≥60 years,the T/T,C/T genotypes and T allele frequency were higher in PD group (196 cases) than in control group (196 cases) (25.5％ vs.20.9％,52.0％ vs.44.4％ and 51.5％ vs.43.1％),for genotype:P=0.027,allele:P=0.018.Between the Uygur versus Han nationality population,the T/T,C/T genotype and T allele frequency in the Uygurs were lower than in the Hans (15.4％ vs.30.4 ％,45.6％ vs.50.5％ and 38.2％ vs.55.7％),for genotype:P =0.000,allele:P =0.000.Conclusions The SNP rs3822086 site of SNCA gene may be a potential susceptibility site of IPD patients over the age of 60 years in Xinjiang,and rs3822086C/T + T/T is susceptible genotypes and rs3822086T is susceptible alleles.The distribution of rs3822086 polymorphism of SNCA might have a significant difference between the Xinjiang Uygur and Han populations.