Research Papers: Gerotarget (Focus on Aging):
NFE2L2 variations reduce antioxidant response in patients with Parkinson disease
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YaXing Gui1, LiShan Zhang1, Wen Lv1, WenMing Zhang1, JinJia Zhao1 and XingYue Hu1
1 Department of Neurology, Sir Run Run Shaw Hospital, Affiliated with School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
Yaxing Gui, email:
Keywords: Parkinson disease, polymorphism, oxidative stress, Gerotarget
Received: October 21, 2015 Accepted: January 24, 2016 Published: February 12, 2016
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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