Synergistic effect of two oxidative stress-related genes (heme oxygenase-1 and GSK3β) on the risk of Parkinson’s disease

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.