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.
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: José A G Agúndez; Elena García-Martín; Carmen Martínez; Julián Benito-León; Jorge Millán-Pascual; María Díaz-Sánchez; Patricia Calleja; Diana Pisa; Laura Turpín-Fenoll; Hortensia Alonso-Navarro; Pau Pastor; Sara Ortega-Cubero; Lucía Ayuso-Peralta; Dolores Torrecillas; Esteban García-Albea; José Francisco Plaza-Nieto; Félix Javier Jiménez-Jiménez Journal: Sci Rep Date: 2016-02-12 Impact factor: 4.379
Authors: Pedro Ayuso; José A G Agúndez; Hortensia Alonso-Navarro; Carmen Martínez; Julián Benito-León; Sara Ortega-Cubero; Oswaldo Lorenzo-Betancor; Pau Pastor; Tomás López-Alburquerque; Elena García-Martín; Félix J Jiménez-Jiménez Journal: Medicine (Baltimore) Date: 2015-06 Impact factor: 1.889
Authors: Pedro Ayuso; Carmen Martínez; Pau Pastor; Oswaldo Lorenzo-Betancor; Antonio Luengo; Félix J Jiménez-Jiménez; Hortensia Alonso-Navarro; José A G Agúndez; Elena García-Martín Journal: Front Cell Neurosci Date: 2014-09-24 Impact factor: 5.505
Authors: Elena García-Martín; Félix Javier Jiménez-Jiménez; Hortensia Alonso-Navarro; Carmen Martínez; Martín Zurdo; Laura Turpín-Fenoll; Jorge Millán-Pascual; Teresa Adeva-Bartolomé; Esther Cubo; Francisco Navacerrada; Ana Rojo-Sebastián; Lluisa Rubio; Sara Ortega-Cubero; Pau Pastor; Marisol Calleja; José Francisco Plaza-Nieto; Belén Pilo-de-la-Fuente; Margarita Arroyo-Solera; Esteban García-Albea; José A G Agúndez Journal: Medicine (Baltimore) Date: 2015-08 Impact factor: 1.817