Journal
ONCOTARGET
Volume 7, Issue 10, Pages 10756-10764Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.7353
Keywords
Parkinson disease; polymorphism; oxidative stress; Gerotarget
Categories
Funding
- Zhejiang Provincial Natural Science Foundation of China [Q14H090011]
- Zhejiang Province Medicine Health General Research Program [2013KYA114]
- National Natural Science Foundation of China [81401038]
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Oxidative stress has been recognized as a risk factor of Parkinson's disease (PD) development. We hypothesized that decreased function of the nuclear factor (erythroid-derived 2)-like 2 (NFE2L2)-antioxidant response element (ARE) pathway might predispose to Parkinsonism. A case-control study was performed between NFE2L2 Single Nucleotide Polymorphism (SNP) and PD in a cohort of 765 unrelated patients with diagnosis of PD and 489 matched normal individuals. We found that c.351T>A, D117E (P = 0.003, OR = 2.8) and c.351T>A, D117E (P = 0.012, OR = 1.9) were significantly associated with PD. The risk allele of both polymorphisms showed a high frequency in our PD sample (c.351A: 19.7% and c.423T: 7.8%). The association between both c.351T>A and c.423G>T and PD was further confirmed in an independent case-control cohort consisting of 210 individuals with PD and 148 normal controls. We further found that over expression of D117E and Q141H variants of NFE2L2 reduced target genes expression of Glutathione S-transferase Pi 1 (GSTP1), Glutathione S-transferase Mu 1 (GSTM1), and Heme oxygenase 1 (HO-1) genes. NFE2L2 D117E and Q141H impaired activation of ARE-driven transcriptional activity. Our findings indicate that NFE2L2 may play an important role in the pathogenesis of PD in Chinese populations.
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