An association study between Heme oxygenase-1 genetic variants and Parkinson´s disease
AbstractThe 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 Parkin...
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doaj-e12ea3da115c4eb982f12512bb3a938f2020-11-24T23:27:08ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022014-09-01810.3389/fncel.2014.00298105744An association study between Heme oxygenase-1 genetic variants and Parkinson´s diseasePedro eAyuso0Pedro eAyuso1Carmen eMartinez2Carmen eMartinez3Pau ePastor4Pau ePastor5Pau ePastor6Oswaldo eLorenzo-Betancor7Oswaldo eLorenzo-Betancor8Antonio eLuengo9Félix Javier eJiménez-Jiménez10Hortensia eAlonso11José A G Agúndez12José A G Agúndez13Elena eGarcía-Martín14Elena eGarcía-Martín15Universidad de ExtremaduraRIRAAF/ RETICS, Redes Temáticas de Investigación Cooperativa en Salud, Instituto de Salud Carlos IIIRIRAAF/ RETICS, Redes Temáticas de Investigación Cooperativa en Salud, Instituto de Salud Carlos IIIUniversidad de ExtremaduraUniversidad de NavarraUniversidad de NavarraCIBERNED, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos IIIUniversidad de NavarraUniversidad de NavarraUniversidad de ExtremaduraHospital Universitario del SuresteHospital Universitario del SuresteRIRAAF/ RETICS, Redes Temáticas de Investigación Cooperativa en Salud, Instituto de Salud Carlos IIIUniversidad de ExtremaduraUniversidad de ExtremaduraRIRAAF/ RETICS, Redes Temáticas de Investigación Cooperativa en Salud, Instituto de Salud Carlos IIIAbstractThe 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 common HMOX1 gene variants 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.http://journal.frontiersin.org/Journal/10.3389/fncel.2014.00298/fullBlood-Brain Barrierheme oxygenaseParkinson’s diseasebiomarkerspolymorphismsiron homeostasis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Pedro eAyuso Pedro eAyuso Carmen eMartinez Carmen eMartinez Pau ePastor Pau ePastor Pau ePastor Oswaldo eLorenzo-Betancor Oswaldo eLorenzo-Betancor Antonio eLuengo Félix Javier eJiménez-Jiménez Hortensia eAlonso José A G Agúndez José A G Agúndez Elena eGarcía-Martín Elena eGarcía-Martín |
spellingShingle |
Pedro eAyuso Pedro eAyuso Carmen eMartinez Carmen eMartinez Pau ePastor Pau ePastor Pau ePastor Oswaldo eLorenzo-Betancor Oswaldo eLorenzo-Betancor Antonio eLuengo Félix Javier eJiménez-Jiménez Hortensia eAlonso José A G Agúndez José A G Agúndez Elena eGarcía-Martín Elena eGarcía-Martín An association study between Heme oxygenase-1 genetic variants and Parkinson´s disease Frontiers in Cellular Neuroscience Blood-Brain Barrier heme oxygenase Parkinson’s disease biomarkers polymorphisms iron homeostasis |
author_facet |
Pedro eAyuso Pedro eAyuso Carmen eMartinez Carmen eMartinez Pau ePastor Pau ePastor Pau ePastor Oswaldo eLorenzo-Betancor Oswaldo eLorenzo-Betancor Antonio eLuengo Félix Javier eJiménez-Jiménez Hortensia eAlonso José A G Agúndez José A G Agúndez Elena eGarcía-Martín Elena eGarcía-Martín |
author_sort |
Pedro eAyuso |
title |
An association study between Heme oxygenase-1 genetic variants and Parkinson´s disease |
title_short |
An association study between Heme oxygenase-1 genetic variants and Parkinson´s disease |
title_full |
An association study between Heme oxygenase-1 genetic variants and Parkinson´s disease |
title_fullStr |
An association study between Heme oxygenase-1 genetic variants and Parkinson´s disease |
title_full_unstemmed |
An association study between Heme oxygenase-1 genetic variants and Parkinson´s disease |
title_sort |
association study between heme oxygenase-1 genetic variants and parkinson´s disease |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cellular Neuroscience |
issn |
1662-5102 |
publishDate |
2014-09-01 |
description |
AbstractThe 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 common HMOX1 gene variants 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. |
topic |
Blood-Brain Barrier heme oxygenase Parkinson’s disease biomarkers polymorphisms iron homeostasis |
url |
http://journal.frontiersin.org/Journal/10.3389/fncel.2014.00298/full |
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