MovDisordV3, Main, Exploration, bibRecord, 000A41

DNA Methylation of MAPT Gene in Parkinson's Disease Cohorts and Modulation by Vitamin E In Vitro

Identifieur interne : 000A41 ( Main/Exploration ); précédent : 000A40; suivant : 000A42

DNA Methylation of MAPT Gene in Parkinson's Disease Cohorts and Modulation by Vitamin E In Vitro

Auteurs : Kirsten G. Coupland [Australie] ; Goerge D. Mellick [Australie] ; Peter A. Silburn [Australie] ; Karen Mather [Australie] ; Nicola J. Armstrong [Australie] ; Perminder S. Sachdev [Australie] ; Henry Brodaty [Australie] ; Yue Huang [Australie] ; Glenda M. Halliday [Australie] ; Marianne Hallupp [Australie] ; Woojin S. Kim [Australie] ; Carol Dobson-Stone [Australie] ; John B. J. Kwok [Australie]

Source :

Movement disorders : official journal of the Movement Disorder Society [ 0885-3185 ] ; 2013.

RBID : PMC:4074263

English descriptors

KwdEn :
- Adult, Aged, Aged, 80 and over, Antioxidants (pharmacology), Brain (metabolism), Cell Line, Tumor, Cohort Studies, DNA Methylation (drug effects), DNA Methylation (genetics), Female, Genotype, Humans, Leukocytes, Mononuclear (drug effects), Male, Middle Aged, Neuroblastoma (pathology), Parkinson Disease (genetics), Parkinson Disease (pathology), Promoter Regions, Genetic, Transfection, Vitamin E (pharmacology), tau Proteins (genetics).
MESH :
- chemical , genetics : tau Proteins.
- chemical , pharmacology : Antioxidants, Vitamin E.
- drug effects : DNA Methylation, Leukocytes, Mononuclear.
- genetics : DNA Methylation, Parkinson Disease.
- metabolism : Brain.
- pathology : Neuroblastoma, Parkinson Disease.
- Adult, Aged, Aged, 80 and over, Cell Line, Tumor, Cohort Studies, Female, Genotype, Humans, Male, Middle Aged, Promoter Regions, Genetic, Transfection.

Abstract

Background

Parkinson's disease (PD) is a neurodegenerative disorder for which environmental factors influence disease risk and may act via an epigenetic mechanism. The microtubule-associated protein tau (MAPT) is a susceptibility gene for idiopathic PD.

Methods

Methylation levels were determined by pyrosequencing of bisulfite treated DNA in a leukocyte cohort (358 PD and 1084 controls) and two brain cohorts (Brain1 comprising 69 cerebellum controls, Brain2 comprising 3 brain regions from 28 PD and 12 controls). In vitro assays involved the transfection of methylated promoter-luciferase constructs or treatment with an exogenous micronutrient.

Results

In normal leukocytes, MAPT H1/H2 diplotype and gender were predictors of MAPT methylation. Haplotype-specific pyrosequencing confirmed H1 haplotype to have higher methylation than H2 in normal leukocyte and brain tissues. MAPT methylation was negatively associated with MAPT expression in Brain1 cohort and transfected cells. Methylation levels differed between three normal brain regions (Brain2, putamen > cerebellum > anterior cingulate cortex). In PD samples, age at onset was positively associated with MAPT methylation in leukocytes. Moreover, there was hypermethylation in the cerebellum and hypomethylation in the putamen of PD patients compared with controls (Brain2 cohort). Finally, leukocyte methylation status was positively associated with blood Vitamin E levels, the effect being more significant in H2 haplotype carriers; this result was confirmed in cells exposed to 100 mM Vitamin E.

Conclusions

The significant effects of gender, diplotype and brain region suggest that hypermethylation of the MAPT is neuroprotective by reducing MAPT expression. Vitamin E effect on MAPT represents a possible gene-environment interaction.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4074263

DOI: 10.1002/mds.25784
PubMed: 24375821
PubMed Central: 4074263

Affiliations:

Australie

Le document en format XML

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 Gene in Parkinson's Disease Cohorts and Modulation by Vitamin E <italic>In Vitro</italic>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">DNA Methylation of <italic>MAPT</italic>
 Gene in Parkinson's Disease Cohorts and Modulation by Vitamin E <italic>In Vitro</italic>
</title>
<author><name sortKey="Coupland, Kirsten G" sort="Coupland, Kirsten G" uniqKey="Coupland K" first="Kirsten G." last="Coupland">Kirsten G. Coupland</name>
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<author><name sortKey="Mellick, Goerge D" sort="Mellick, Goerge D" uniqKey="Mellick G" first="Goerge D." last="Mellick">Goerge D. Mellick</name>
<affiliation wicri:level="1"><nlm:aff id="A3">Eskitis Institute for Cell and Molecular Therapies, Griffith University, Brisbane, Qld, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
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<author><name sortKey="Silburn, Peter A" sort="Silburn, Peter A" uniqKey="Silburn P" first="Peter A." last="Silburn">Peter A. Silburn</name>
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<author><name sortKey="Mather, Karen" sort="Mather, Karen" uniqKey="Mather K" first="Karen" last="Mather">Karen Mather</name>
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<author><name sortKey="Armstrong, Nicola J" sort="Armstrong, Nicola J" uniqKey="Armstrong N" first="Nicola J." last="Armstrong">Nicola J. Armstrong</name>
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<country xml:lang="fr">Australie</country>
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<author><name sortKey="Sachdev, Perminder S" sort="Sachdev, Perminder S" uniqKey="Sachdev P" first="Perminder S." last="Sachdev">Perminder S. Sachdev</name>
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<affiliation wicri:level="1"><nlm:aff id="A8">Neuropsychiatric Institute (NPI), Prince of Wales Hospital, Sydney, NSW, Australia</nlm:aff>
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<author><name sortKey="Brodaty, Henry" sort="Brodaty, Henry" uniqKey="Brodaty H" first="Henry" last="Brodaty">Henry Brodaty</name>
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<affiliation wicri:level="1"><nlm:aff id="A9">Aged Care Psychiatry, Prince of Wales Hospital, Sydney, NSW, Australia</nlm:aff>
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<author><name sortKey="Huang, Yue" sort="Huang, Yue" uniqKey="Huang Y" first="Yue" last="Huang">Yue Huang</name>
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<author><name sortKey="Halliday, Glenda M" sort="Halliday, Glenda M" uniqKey="Halliday G" first="Glenda M." last="Halliday">Glenda M. Halliday</name>
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<author><name sortKey="Hallupp, Marianne" sort="Hallupp, Marianne" uniqKey="Hallupp M" first="Marianne" last="Hallupp">Marianne Hallupp</name>
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<country xml:lang="fr">Australie</country>
<wicri:regionArea>Neuroscience Research Australia, Sydney, NSW</wicri:regionArea>
<wicri:noRegion>NSW</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Kim, Woojin S" sort="Kim, Woojin S" uniqKey="Kim W" first="Woojin S." last="Kim">Woojin S. Kim</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Neuroscience Research Australia, Sydney, NSW, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Neuroscience Research Australia, Sydney, NSW</wicri:regionArea>
<wicri:noRegion>NSW</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A2">School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>School of Medical Sciences, University of New South Wales, Sydney, NSW</wicri:regionArea>
<wicri:noRegion>NSW</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Dobson Stone, Carol" sort="Dobson Stone, Carol" uniqKey="Dobson Stone C" first="Carol" last="Dobson-Stone">Carol Dobson-Stone</name>
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<country xml:lang="fr">Australie</country>
<wicri:regionArea>Neuroscience Research Australia, Sydney, NSW</wicri:regionArea>
<wicri:noRegion>NSW</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A2">School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>School of Medical Sciences, University of New South Wales, Sydney, NSW</wicri:regionArea>
<wicri:noRegion>NSW</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Kwok, John B J" sort="Kwok, John B J" uniqKey="Kwok J" first="John B. J." last="Kwok">John B. J. Kwok</name>
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<country xml:lang="fr">Australie</country>
<wicri:regionArea>Neuroscience Research Australia, Sydney, NSW</wicri:regionArea>
<wicri:noRegion>NSW</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A2">School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>School of Medical Sciences, University of New South Wales, Sydney, NSW</wicri:regionArea>
<wicri:noRegion>NSW</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title>
<idno type="ISSN">0885-3185</idno>
<idno type="eISSN">1531-8257</idno>
<imprint><date when="2013">2013</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term>
<term>Aged</term>
<term>Aged, 80 and over</term>
<term>Antioxidants (pharmacology)</term>
<term>Brain (metabolism)</term>
<term>Cell Line, Tumor</term>
<term>Cohort Studies</term>
<term>DNA Methylation (drug effects)</term>
<term>DNA Methylation (genetics)</term>
<term>Female</term>
<term>Genotype</term>
<term>Humans</term>
<term>Leukocytes, Mononuclear (drug effects)</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Neuroblastoma (pathology)</term>
<term>Parkinson Disease (genetics)</term>
<term>Parkinson Disease (pathology)</term>
<term>Promoter Regions, Genetic</term>
<term>Transfection</term>
<term>Vitamin E (pharmacology)</term>
<term>tau Proteins (genetics)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>tau Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antioxidants</term>
<term>Vitamin E</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>DNA Methylation</term>
<term>Leukocytes, Mononuclear</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>DNA Methylation</term>
<term>Parkinson Disease</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Brain</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Neuroblastoma</term>
<term>Parkinson Disease</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Adult</term>
<term>Aged</term>
<term>Aged, 80 and over</term>
<term>Cell Line, Tumor</term>
<term>Cohort Studies</term>
<term>Female</term>
<term>Genotype</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Promoter Regions, Genetic</term>
<term>Transfection</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><sec id="S1"><title>Background</title>
<p id="P1">Parkinson's disease (PD) is a neurodegenerative disorder for which environmental factors influence disease risk and may act via an epigenetic mechanism. The microtubule-associated protein tau (<italic>MAPT</italic>
) is a susceptibility gene for idiopathic PD.</p>
</sec>
<sec id="S2"><title>Methods</title>
<p id="P2">Methylation levels were determined by pyrosequencing of bisulfite treated DNA in a leukocyte cohort (358 PD and 1084 controls) and two brain cohorts (Brain1 comprising 69 cerebellum controls, Brain2 comprising 3 brain regions from 28 PD and 12 controls). <italic>In vitro</italic>
 assays involved the transfection of methylated promoter-luciferase constructs or treatment with an exogenous micronutrient.</p>
</sec>
<sec id="S3"><title>Results</title>
<p id="P3">In normal leukocytes, <italic>MAPT</italic>
 H1/H2 diplotype and gender were predictors of <italic>MAPT</italic>
 methylation. Haplotype-specific pyrosequencing confirmed H1 haplotype to have higher methylation than H2 in normal leukocyte and brain tissues. <italic>MAPT</italic>
 methylation was negatively associated with <italic>MAPT</italic>
 expression in Brain1 cohort and transfected cells. Methylation levels differed between three normal brain regions (Brain2, putamen > cerebellum > anterior cingulate cortex). In PD samples, age at onset was positively associated with <italic>MAPT</italic>
 methylation in leukocytes. Moreover, there was hypermethylation in the cerebellum and hypomethylation in the putamen of PD patients compared with controls (Brain2 cohort). Finally, leukocyte methylation status was positively associated with blood Vitamin E levels, the effect being more significant in H2 haplotype carriers; this result was confirmed in cells exposed to 100 mM Vitamin E.</p>
</sec>
<sec id="S4"><title>Conclusions</title>
<p id="P4">The significant effects of gender, diplotype and brain region suggest that hypermethylation of the <italic>MAPT</italic>
 is neuroprotective by reducing <italic>MAPT</italic>
 expression. Vitamin E effect on <italic>MAPT</italic>
 represents a possible gene-environment interaction.</p>
</sec>
</div>
</front>
</TEI>
<affiliations><list><country><li>Australie</li>
</country>
</list>
<tree><country name="Australie"><noRegion><name sortKey="Coupland, Kirsten G" sort="Coupland, Kirsten G" uniqKey="Coupland K" first="Kirsten G." last="Coupland">Kirsten G. Coupland</name>
</noRegion>
<name sortKey="Armstrong, Nicola J" sort="Armstrong, Nicola J" uniqKey="Armstrong N" first="Nicola J." last="Armstrong">Nicola J. Armstrong</name>
<name sortKey="Armstrong, Nicola J" sort="Armstrong, Nicola J" uniqKey="Armstrong N" first="Nicola J." last="Armstrong">Nicola J. Armstrong</name>
<name sortKey="Armstrong, Nicola J" sort="Armstrong, Nicola J" uniqKey="Armstrong N" first="Nicola J." last="Armstrong">Nicola J. Armstrong</name>
<name sortKey="Brodaty, Henry" sort="Brodaty, Henry" uniqKey="Brodaty H" first="Henry" last="Brodaty">Henry Brodaty</name>
<name sortKey="Brodaty, Henry" sort="Brodaty, Henry" uniqKey="Brodaty H" first="Henry" last="Brodaty">Henry Brodaty</name>
<name sortKey="Coupland, Kirsten G" sort="Coupland, Kirsten G" uniqKey="Coupland K" first="Kirsten G." last="Coupland">Kirsten G. Coupland</name>
<name sortKey="Dobson Stone, Carol" sort="Dobson Stone, Carol" uniqKey="Dobson Stone C" first="Carol" last="Dobson-Stone">Carol Dobson-Stone</name>
<name sortKey="Dobson Stone, Carol" sort="Dobson Stone, Carol" uniqKey="Dobson Stone C" first="Carol" last="Dobson-Stone">Carol Dobson-Stone</name>
<name sortKey="Halliday, Glenda M" sort="Halliday, Glenda M" uniqKey="Halliday G" first="Glenda M." last="Halliday">Glenda M. Halliday</name>
<name sortKey="Halliday, Glenda M" sort="Halliday, Glenda M" uniqKey="Halliday G" first="Glenda M." last="Halliday">Glenda M. Halliday</name>
<name sortKey="Hallupp, Marianne" sort="Hallupp, Marianne" uniqKey="Hallupp M" first="Marianne" last="Hallupp">Marianne Hallupp</name>
<name sortKey="Huang, Yue" sort="Huang, Yue" uniqKey="Huang Y" first="Yue" last="Huang">Yue Huang</name>
<name sortKey="Huang, Yue" sort="Huang, Yue" uniqKey="Huang Y" first="Yue" last="Huang">Yue Huang</name>
<name sortKey="Kim, Woojin S" sort="Kim, Woojin S" uniqKey="Kim W" first="Woojin S." last="Kim">Woojin S. Kim</name>
<name sortKey="Kim, Woojin S" sort="Kim, Woojin S" uniqKey="Kim W" first="Woojin S." last="Kim">Woojin S. Kim</name>
<name sortKey="Kwok, John B J" sort="Kwok, John B J" uniqKey="Kwok J" first="John B. J." last="Kwok">John B. J. Kwok</name>
<name sortKey="Kwok, John B J" sort="Kwok, John B J" uniqKey="Kwok J" first="John B. J." last="Kwok">John B. J. Kwok</name>
<name sortKey="Mather, Karen" sort="Mather, Karen" uniqKey="Mather K" first="Karen" last="Mather">Karen Mather</name>
<name sortKey="Mellick, Goerge D" sort="Mellick, Goerge D" uniqKey="Mellick G" first="Goerge D." last="Mellick">Goerge D. Mellick</name>
<name sortKey="Sachdev, Perminder S" sort="Sachdev, Perminder S" uniqKey="Sachdev P" first="Perminder S." last="Sachdev">Perminder S. Sachdev</name>
<name sortKey="Sachdev, Perminder S" sort="Sachdev, Perminder S" uniqKey="Sachdev P" first="Perminder S." last="Sachdev">Perminder S. Sachdev</name>
<name sortKey="Silburn, Peter A" sort="Silburn, Peter A" uniqKey="Silburn P" first="Peter A." last="Silburn">Peter A. Silburn</name>
</country>
</tree>
</affiliations>
</record>

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Movement Disorders (revue)

DNA Methylation of MAPT Gene in Parkinson's Disease Cohorts and Modulation by Vitamin E In Vitro

DNA Methylation of MAPT Gene in Parkinson's Disease Cohorts and Modulation by Vitamin E In Vitro

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