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Synergistic effect of two oxidative stress‐related genes (heme oxygenase‐1 and GSK3β) on the risk of Parkinson’s disease
Author(s) -
Infante J.,
GarcíaGorostiaga I.,
SánchezJuan P.,
Sierra M.,
MartínGurpegui J. L.,
Terrazas J.,
Mateo I.,
RodríguezRodríguez E.,
Berciano J.,
Combarros O.
Publication year - 2010
Publication title -
european journal of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 124
eISSN - 1468-1331
pISSN - 1351-5101
DOI - 10.1111/j.1468-1331.2009.02908.x
Subject(s) - heme oxygenase , oxidative stress , gsk 3 , medicine , pathogenesis , parkinson's disease , antioxidant , genotype , endocrinology , disease , oxidative phosphorylation , downregulation and upregulation , heme , bioinformatics , gene , genetics , kinase , biology , biochemistry , enzyme
Background: Oxidative stress is a central factor in the pathogenesis of Parkinson’s disease (PD). Heme oxygenase‐1 (HO‐1) is an antioxidant protein expressed in response to oxidative challenge, and its expression levels are inversely correlated with glycogen synthase kinase‐3β (GSK3β) activity. Underexpression of HO‐1 in concert with an upregulation of GSK3β would result in a less effective antioxidant response and might increase the risk of PD. Methods: We examined two functional polymorphism in the promoter regions of HO‐1 (−413, rs2071746) and GSK3β (−157, rs6438552) in a group of 251 Spanish patients with PD and 234 controls. Results: Subjects carrying both the HO‐1 (−413, rs2071746) TT genotype and the GSK3β (−157, rs6438552) TT genotype had a four times higher risk of developing PD than subjects without these genotypes (adjusted by age and sex OR = 4.12; 95% CI = 1.45–11.71; Bonferroni corrected P = 0.024). Conclusions: Considering synergistic effects between polymorphisms in oxidative stress‐related genes may help in determining the risk profile for PD.