title: An association study between Heme oxygenase-1 genetic variants and Parkinson's disease.
abstract: The blood-brain barrier (BBB) supplies brain tissues with nutrients, filters harmful compounds from the brain back to the bloodstream, and plays a key role in iron homeostasis in the human brain. Disruptions of the BBB are associated with several neurodegenerative conditions including Parkinson's disease (PD). Oxidative stress, iron deposition and mitochondrial impaired function are considered as risk factors for degeneration of the central nervous system. Heme oxygenase (HMOX) degrades heme ring to biliverdin, free ferrous iron and carbon monoxide being the rate-limiting activity in heme catabolism. The isoform HMOX1 is highly inducible in response to reactive oxygen species, which induce an increase in BBB permeability and impair its pathophysiology. Consequently, an over- expression of this enzyme may contribute to the marked iron deposition found in PD. We analyzed the HMOX1 SNPs rs2071746, rs2071747, and rs9282702, a microsatellite (GT) n polymorphism and copy number variations in 691 patients suffering from PD and 766 healthy control individuals. Copy number variations in the HMOX1 gene exist, but these do not seem to be associated with PD risk. In contrast two polymorphisms that modify the transcriptional activity of the gene, namely a VNTR (GT) n and the SNP rs2071746, are strongly associated with PD risk, particularly with the classic PD phenotype and with early onset of the disease. This study indicates that HMOX1 gene variants are associated to the risk of developing some forms of PD, thus adding new information that supports association of HMOX gene variations with PD risk.
authors.affiliation: Department of Biochemistry, Molecular Biology, and Genetic, University of Extremadura Cáceres, Spain ; Redes Temáticas de Investigación Cooperativa en Salud (RIRAAF/RETICS), Instituto de Salud Carlos III Madrid, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Ayuso
authors.affiliation: Redes Temáticas de Investigación Cooperativa en Salud (RIRAAF/RETICS), Instituto de Salud Carlos III Madrid, Spain ; Department of Pharmacology, University of Extremadura Cáceres, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Martínez
authors.affiliation: Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research (CIMA), University of Navarra Pamplona, Spain ; Department of Neurology, School of Medicine, Clínica Universidad de Navarra, University of Navarra Pamplona, Spain ; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III Madrid, Spain.
authors.forename: Pau
authors.initials: P
authors.lastname: Pastor
authors.affiliation: Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research (CIMA), University of Navarra Pamplona, Spain ; Department of Neurology, School of Medicine, Clínica Universidad de Navarra, University of Navarra Pamplona, Spain.
authors.forename: Oswaldo
authors.initials: O
authors.lastname: Lorenzo-Betancor
authors.affiliation: Department of Pharmacology, University of Extremadura Cáceres, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Luengo
authors.affiliation: Section of Neurology, Hospital Universitario del Sureste Madrid, Spain.
authors.forename: Félix J
authors.initials: FJ
authors.lastname: Jiménez-Jiménez
authors.affiliation: Section of Neurology, Hospital Universitario del Sureste Madrid, Spain.
authors.forename: Hortensia
authors.initials: H
authors.lastname: Alonso-Navarro
authors.affiliation: Redes Temáticas de Investigación Cooperativa en Salud (RIRAAF/RETICS), Instituto de Salud Carlos III Madrid, Spain ; Department of Pharmacology, University of Extremadura Cáceres, Spain.
authors.forename: José A G
authors.initials: JA
authors.lastname: Agúndez
authors.affiliation: Department of Biochemistry, Molecular Biology, and Genetic, University of Extremadura Cáceres, Spain ; Redes Temáticas de Investigación Cooperativa en Salud (RIRAAF/RETICS), Instituto de Salud Carlos III Madrid, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: García-Martín
keywords: Heme oxygenase; Parkinson's disease; biomarkers; blood-brain barrier; copy number variations; iron homeostasis; polymorphisms