title: Synergistic effect of two oxidative stress-related genes (heme oxygenase-1 and GSK3β) on the risk of Parkinson's disease.
abstract: 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-3beta (GSK3beta) activity. Underexpression of HO-1 in concert with an upregulation of GSK3beta 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 GSK3beta (-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 GSK3beta (-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.
authors.affiliation: Neurology Service and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), "Marqués de Valdecilla" University Hospital (University of Cantabria), Santander, Spain. jinfante@humv.es
authors.forename: J
authors.initials: J
authors.lastname: Infante
authors.forename: I
authors.initials: I
authors.lastname: García-Gorostiaga
authors.forename: P
authors.initials: P
authors.lastname: Sánchez-Juan
authors.forename: M
authors.initials: M
authors.lastname: Sierra
authors.forename: J L
authors.initials: JL
authors.lastname: Martín-Gurpegui
authors.forename: J
authors.initials: J
authors.lastname: Terrazas
authors.forename: I
authors.initials: I
authors.lastname: Mateo
authors.forename: E
authors.initials: E
authors.lastname: Rodríguez-Rodríguez
authors.forename: J
authors.initials: J
authors.lastname: Berciano
authors.forename: O
authors.initials: O
authors.lastname: Combarros
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics*; D000071679:Glycogen Synthase Kinase 3 beta; D051547:Heme Oxygenase-1 / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000235:genetics*; D010300:Parkinson Disease / Q000201:enzymology* / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D018570:Risk Assessment
chemical_list: D051547:Heme Oxygenase-1; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3