AustralieFrV1, Ncbi, Merge, bibRecord, 002851

A rare P2X7 variant Arg307Gln with absent pore formation function protects against neuroinflammation in multiple sclerosis.

Identifieur interne : 002851 ( Ncbi/Merge ); précédent : 002850; suivant : 002852

A rare P2X7 variant Arg307Gln with absent pore formation function protects against neuroinflammation in multiple sclerosis.

Auteurs : Ben J. Gu [Australie] ; Judith Field [Australie] ; Sébastien Dutertre [France] ; Amber Ou [Australie] ; Trevor J. Kilpatrick [Australie] ; Jeannette Lechner-Scott [Australie] ; Rodney Scott [Australie] ; Rodney Lea [Australie] ; Bruce V. Taylor [Australie] ; Jim Stankovich [Australie] ; Helmut Butzkueven [Australie] ; Melissa Gresle [Australie] ; Simon M. Laws [Australie] ; Steven Petrou [Australie] ; Sabine Hoffjan [Allemagne] ; Denis A. Akkad [Allemagne] ; Colin A. Graham [Royaume-Uni] ; Stanley Hawkins [Royaume-Uni] ; Anna Glaser [Suède] ; Sahl Khalid Bedri [Suède] ; Jan Hillert [Suède] ; Carlos Matute ; Alfredo Antiguedad [Espagne] ; James S. Wiley [Australie]

Source :

Human molecular genetics [ 1460-2083 ] ; 2015.

RBID : pubmed:26188005

Descripteurs français

English descriptors

KwdEn :
- Adenosine Triphosphate (metabolism), Amino Acid Substitution, Arginine (metabolism), Australasia, Binding Sites, European Continental Ancestry Group (genetics), Genetic Association Studies, Genetic Predisposition to Disease, Glutamine (metabolism), Humans, Models, Molecular, Multiple Sclerosis (genetics), Multiple Sclerosis (metabolism), Multiple Sclerosis (pathology), Receptors, Purinergic P2X7 (chemistry), Receptors, Purinergic P2X7 (genetics), Receptors, Purinergic P2X7 (metabolism).
MESH :
- chemical , chemistry : Receptors, Purinergic P2X7.
- chemical , genetics : Receptors, Purinergic P2X7.
- chemical , metabolism : Adenosine Triphosphate, Arginine, Glutamine, Receptors, Purinergic P2X7.
- geographic : Australasia.
- genetics : European Continental Ancestry Group, Multiple Sclerosis.
- metabolism : Multiple Sclerosis.
- pathology : Multiple Sclerosis.
- Amino Acid Substitution, Binding Sites, Genetic Association Studies, Genetic Predisposition to Disease, Humans, Models, Molecular.

Abstract

Multiple sclerosis (MS) is a chronic relapsing-remitting inflammatory disease of the central nervous system characterized by oligodendrocyte damage, demyelination and neuronal death. Genetic association studies have shown a 2-fold or greater prevalence of the HLA-DRB1*1501 allele in the MS population compared with normal Caucasians. In discovery cohorts of Australasian patients with MS (total 2941 patients and 3008 controls), we examined the associations of 12 functional polymorphisms of P2X7, a microglial/macrophage receptor with proinflammatory effects when activated by extracellular adenosine triphosphate (ATP). In discovery cohorts, rs28360457, coding for Arg307Gln was associated with MS and combined analysis showed a 2-fold lower minor allele frequency compared with controls (1.11% for MS and 2.15% for controls, P = 0.0000071). Replication analysis of four independent European MS case-control cohorts (total 2140 cases and 2634 controls) confirmed this association [odds ratio (OR) = 0.69, P = 0.026]. A meta-analysis of all Australasian and European cohorts indicated that Arg307Gln confers a 1.8-fold protective effect on MS risk (OR = 0.57, P = 0.0000024). Fresh human monocytes heterozygous for Arg307Gln have >85% loss of 'pore' function of the P2X7 receptor measured by ATP-induced ethidium uptake. Analysis shows Arg307Gln always occurred with 270His suggesting a single 307Gln-270His haplotype that confers dominant negative effects on P2X7 function and protection against MS. Modeling based on the homologous zP2X4 receptor showed Arg307 is located in a region rich in basic residues located only 12 Å from the ligand binding site. Our data show the protective effect against MS of a rare genetic variant of P2RX7 with heterozygotes showing near absent proinflammatory 'pore' function.

DOI: 10.1093/hmg/ddv278
PubMed: 26188005

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<author><name sortKey="Taylor, Bruce V" sort="Taylor, Bruce V" uniqKey="Taylor B" first="Bruce V" last="Taylor">Bruce V. Taylor</name>
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<author><name sortKey="Hoffjan, Sabine" sort="Hoffjan, Sabine" uniqKey="Hoffjan S" first="Sabine" last="Hoffjan">Sabine Hoffjan</name>
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<author><name sortKey="Akkad, Denis A" sort="Akkad, Denis A" uniqKey="Akkad D" first="Denis A" last="Akkad">Denis A. Akkad</name>
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<author><name sortKey="Graham, Colin A" sort="Graham, Colin A" uniqKey="Graham C" first="Colin A" last="Graham">Colin A. Graham</name>
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<author><name sortKey="Hawkins, Stanley" sort="Hawkins, Stanley" uniqKey="Hawkins S" first="Stanley" last="Hawkins">Stanley Hawkins</name>
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<author><name sortKey="Glaser, Anna" sort="Glaser, Anna" uniqKey="Glaser A" first="Anna" last="Glaser">Anna Glaser</name>
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<author><name sortKey="Bedri, Sahl Khalid" sort="Bedri, Sahl Khalid" uniqKey="Bedri S" first="Sahl Khalid" last="Bedri">Sahl Khalid Bedri</name>
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<author><name sortKey="Hillert, Jan" sort="Hillert, Jan" uniqKey="Hillert J" first="Jan" last="Hillert">Jan Hillert</name>
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<author><name sortKey="Matute, Carlos" sort="Matute, Carlos" uniqKey="Matute C" first="Carlos" last="Matute">Carlos Matute</name>
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</affiliation>
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<author><name sortKey="Antiguedad, Alfredo" sort="Antiguedad, Alfredo" uniqKey="Antiguedad A" first="Alfredo" last="Antiguedad">Alfredo Antiguedad</name>
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<country wicri:rule="url">Australie</country>
<wicri:regionArea>Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia</wicri:regionArea>
<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">A rare P2X7 variant Arg307Gln with absent pore formation function protects against neuroinflammation in multiple sclerosis.</title>
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<author><name sortKey="Lechner Scott, Jeannette" sort="Lechner Scott, Jeannette" uniqKey="Lechner Scott J" first="Jeannette" last="Lechner-Scott">Jeannette Lechner-Scott</name>
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<author><name sortKey="Scott, Rodney" sort="Scott, Rodney" uniqKey="Scott R" first="Rodney" last="Scott">Rodney Scott</name>
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<country xml:lang="fr">Australie</country>
<wicri:regionArea>Hunter Medical Research Institute, The University of Newcastle, Newcastle, New South Wales</wicri:regionArea>
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<author><name sortKey="Lea, Rodney" sort="Lea, Rodney" uniqKey="Lea R" first="Rodney" last="Lea">Rodney Lea</name>
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<country xml:lang="fr">Australie</country>
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<author><name sortKey="Taylor, Bruce V" sort="Taylor, Bruce V" uniqKey="Taylor B" first="Bruce V" last="Taylor">Bruce V. Taylor</name>
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<country xml:lang="fr">Australie</country>
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</affiliation>
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<author><name sortKey="Stankovich, Jim" sort="Stankovich, Jim" uniqKey="Stankovich J" first="Jim" last="Stankovich">Jim Stankovich</name>
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<country xml:lang="fr">Australie</country>
<wicri:regionArea>Menzies Institute, University of Tasmania, Hobart, Tasmania</wicri:regionArea>
<wicri:noRegion>Tasmania</wicri:noRegion>
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<author><name sortKey="Hoffjan, Sabine" sort="Hoffjan, Sabine" uniqKey="Hoffjan S" first="Sabine" last="Hoffjan">Sabine Hoffjan</name>
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<country xml:lang="fr">Allemagne</country>
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<author><name sortKey="Hawkins, Stanley" sort="Hawkins, Stanley" uniqKey="Hawkins S" first="Stanley" last="Hawkins">Stanley Hawkins</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Neurology, Belfast Health & Social Care Trust, Northern Ireland, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Neurology, Belfast Health & Social Care Trust, Northern Ireland</wicri:regionArea>
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</affiliation>
</author>
<author><name sortKey="Glaser, Anna" sort="Glaser, Anna" uniqKey="Glaser A" first="Anna" last="Glaser">Anna Glaser</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Clinical Neurosciences, Karolinska Institutet, Stockholm, Sweden.</nlm:affiliation>
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</placeName>
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<country xml:lang="fr">Suède</country>
<wicri:regionArea>Department of Clinical Neurosciences, Karolinska Institutet, Stockholm</wicri:regionArea>
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</placeName>
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<country xml:lang="fr">Suède</country>
<wicri:regionArea>Department of Clinical Neurosciences, Karolinska Institutet, Stockholm</wicri:regionArea>
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<region nuts="2">Svealand</region>
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<author><name sortKey="Matute, Carlos" sort="Matute, Carlos" uniqKey="Matute C" first="Carlos" last="Matute">Carlos Matute</name>
<affiliation><nlm:affiliation>CIBERNED, Achucarro Basque Center for Neuroscience, and Departamento de Neurociencias, Universidad del País Vasco, Leioa, Spain and.</nlm:affiliation>
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<author><name sortKey="Antiguedad, Alfredo" sort="Antiguedad, Alfredo" uniqKey="Antiguedad A" first="Alfredo" last="Antiguedad">Alfredo Antiguedad</name>
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<country xml:lang="fr">Espagne</country>
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<author><name sortKey="Wiley, James S" sort="Wiley, James S" uniqKey="Wiley J" first="James S" last="Wiley">James S. Wiley</name>
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<placeName><settlement type="city">Melbourne</settlement>
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<series><title level="j">Human molecular genetics</title>
<idno type="eISSN">1460-2083</idno>
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<term>Amino Acid Substitution</term>
<term>Arginine (metabolism)</term>
<term>Australasia</term>
<term>Binding Sites</term>
<term>European Continental Ancestry Group (genetics)</term>
<term>Genetic Association Studies</term>
<term>Genetic Predisposition to Disease</term>
<term>Glutamine (metabolism)</term>
<term>Humans</term>
<term>Models, Molecular</term>
<term>Multiple Sclerosis (genetics)</term>
<term>Multiple Sclerosis (metabolism)</term>
<term>Multiple Sclerosis (pathology)</term>
<term>Receptors, Purinergic P2X7 (chemistry)</term>
<term>Receptors, Purinergic P2X7 (genetics)</term>
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<term>Glutamine (métabolisme)</term>
<term>Humains</term>
<term>Modèles moléculaires</term>
<term>Population d'origine européenne (génétique)</term>
<term>Prédisposition génétique à une maladie</term>
<term>Récepteurs purinergiques P2X7 ()</term>
<term>Récepteurs purinergiques P2X7 (génétique)</term>
<term>Récepteurs purinergiques P2X7 (métabolisme)</term>
<term>Sclérose en plaques (anatomopathologie)</term>
<term>Sclérose en plaques (génétique)</term>
<term>Sclérose en plaques (métabolisme)</term>
<term>Sites de fixation</term>
<term>Substitution d'acide aminé</term>
<term>Études d'associations génétiques</term>
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<front><div type="abstract" xml:lang="en">Multiple sclerosis (MS) is a chronic relapsing-remitting inflammatory disease of the central nervous system characterized by oligodendrocyte damage, demyelination and neuronal death. Genetic association studies have shown a 2-fold or greater prevalence of the HLA-DRB1*1501 allele in the MS population compared with normal Caucasians. In discovery cohorts of Australasian patients with MS (total 2941 patients and 3008 controls), we examined the associations of 12 functional polymorphisms of P2X7, a microglial/macrophage receptor with proinflammatory effects when activated by extracellular adenosine triphosphate (ATP). In discovery cohorts, rs28360457, coding for Arg307Gln was associated with MS and combined analysis showed a 2-fold lower minor allele frequency compared with controls (1.11% for MS and 2.15% for controls, P = 0.0000071). Replication analysis of four independent European MS case-control cohorts (total 2140 cases and 2634 controls) confirmed this association [odds ratio (OR) = 0.69, P = 0.026]. A meta-analysis of all Australasian and European cohorts indicated that Arg307Gln confers a 1.8-fold protective effect on MS risk (OR = 0.57, P = 0.0000024). Fresh human monocytes heterozygous for Arg307Gln have >85% loss of 'pore' function of the P2X7 receptor measured by ATP-induced ethidium uptake. Analysis shows Arg307Gln always occurred with 270His suggesting a single 307Gln-270His haplotype that confers dominant negative effects on P2X7 function and protection against MS. Modeling based on the homologous zP2X4 receptor showed Arg307 is located in a region rich in basic residues located only 12 Å from the ligand binding site. Our data show the protective effect against MS of a rare genetic variant of P2RX7 with heterozygotes showing near absent proinflammatory 'pore' function.</div>
</front>
</TEI>
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<DateCreated><Year>2015</Year>
<Month>09</Month>
<Day>16</Day>
</DateCreated>
<DateCompleted><Year>2016</Year>
<Month>07</Month>
<Day>06</Day>
</DateCompleted>
<DateRevised><Year>2015</Year>
<Month>09</Month>
<Day>16</Day>
</DateRevised>
<Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1460-2083</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>24</Volume>
<Issue>19</Issue>
<PubDate><Year>2015</Year>
<Month>Oct</Month>
<Day>01</Day>
</PubDate>
</JournalIssue>
<Title>Human molecular genetics</Title>
<ISOAbbreviation>Hum. Mol. Genet.</ISOAbbreviation>
</Journal>
<ArticleTitle>A rare P2X7 variant Arg307Gln with absent pore formation function protects against neuroinflammation in multiple sclerosis.</ArticleTitle>
<Pagination><MedlinePgn>5644-54</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1093/hmg/ddv278</ELocationID>
<Abstract><AbstractText>Multiple sclerosis (MS) is a chronic relapsing-remitting inflammatory disease of the central nervous system characterized by oligodendrocyte damage, demyelination and neuronal death. Genetic association studies have shown a 2-fold or greater prevalence of the HLA-DRB1*1501 allele in the MS population compared with normal Caucasians. In discovery cohorts of Australasian patients with MS (total 2941 patients and 3008 controls), we examined the associations of 12 functional polymorphisms of P2X7, a microglial/macrophage receptor with proinflammatory effects when activated by extracellular adenosine triphosphate (ATP). In discovery cohorts, rs28360457, coding for Arg307Gln was associated with MS and combined analysis showed a 2-fold lower minor allele frequency compared with controls (1.11% for MS and 2.15% for controls, P = 0.0000071). Replication analysis of four independent European MS case-control cohorts (total 2140 cases and 2634 controls) confirmed this association [odds ratio (OR) = 0.69, P = 0.026]. A meta-analysis of all Australasian and European cohorts indicated that Arg307Gln confers a 1.8-fold protective effect on MS risk (OR = 0.57, P = 0.0000024). Fresh human monocytes heterozygous for Arg307Gln have >85% loss of 'pore' function of the P2X7 receptor measured by ATP-induced ethidium uptake. Analysis shows Arg307Gln always occurred with 270His suggesting a single 307Gln-270His haplotype that confers dominant negative effects on P2X7 function and protection against MS. Modeling based on the homologous zP2X4 receptor showed Arg307 is located in a region rich in basic residues located only 12 Å from the ligand binding site. Our data show the protective effect against MS of a rare genetic variant of P2RX7 with heterozygotes showing near absent proinflammatory 'pore' function.</AbstractText>
<CopyrightInformation>© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Gu</LastName>
<ForeName>Ben J</ForeName>
<Initials>BJ</Initials>
<AffiliationInfo><Affiliation>Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Field</LastName>
<ForeName>Judith</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Dutertre</LastName>
<ForeName>Sébastien</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Institut des Biomolécules Max Mousseron, UMR 5247, Université Montpellier 2-CNRS, Montpellier, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ou</LastName>
<ForeName>Amber</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Kilpatrick</LastName>
<ForeName>Trevor J</ForeName>
<Initials>TJ</Initials>
<AffiliationInfo><Affiliation>Melbourne Neuroscience Institute, University of Melbourne, Parkville, Victoria, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Lechner-Scott</LastName>
<ForeName>Jeannette</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Hunter Medical Research Institute, The University of Newcastle, Newcastle, New South Wales, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Scott</LastName>
<ForeName>Rodney</ForeName>
<Initials>R</Initials>
<AffiliationInfo><Affiliation>Hunter Medical Research Institute, The University of Newcastle, Newcastle, New South Wales, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Lea</LastName>
<ForeName>Rodney</ForeName>
<Initials>R</Initials>
<AffiliationInfo><Affiliation>Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Taylor</LastName>
<ForeName>Bruce V</ForeName>
<Initials>BV</Initials>
<AffiliationInfo><Affiliation>Menzies Institute, University of Tasmania, Hobart, Tasmania, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Stankovich</LastName>
<ForeName>Jim</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Menzies Institute, University of Tasmania, Hobart, Tasmania, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Butzkueven</LastName>
<ForeName>Helmut</ForeName>
<Initials>H</Initials>
<AffiliationInfo><Affiliation>Department of Medicine, University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Gresle</LastName>
<ForeName>Melissa</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Department of Medicine, University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Laws</LastName>
<ForeName>Simon M</ForeName>
<Initials>SM</Initials>
<AffiliationInfo><Affiliation>School of Medical Sciences, Edith Cowan University, Joondalup, Western Australia, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Petrou</LastName>
<ForeName>Steven</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Hoffjan</LastName>
<ForeName>Sabine</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Department of Human Genetics, Ruhr-University Bochum, Bochum, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Akkad</LastName>
<ForeName>Denis A</ForeName>
<Initials>DA</Initials>
<AffiliationInfo><Affiliation>Department of Human Genetics, Ruhr-University Bochum, Bochum, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Graham</LastName>
<ForeName>Colin A</ForeName>
<Initials>CA</Initials>
<AffiliationInfo><Affiliation>Regional Genetics Laboratories, Belfast Health & Social Care Trust, Northern Ireland, UK.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Hawkins</LastName>
<ForeName>Stanley</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Department of Neurology, Belfast Health & Social Care Trust, Northern Ireland, UK.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Glaser</LastName>
<ForeName>Anna</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>Department of Clinical Neurosciences, Karolinska Institutet, Stockholm, Sweden.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Bedri</LastName>
<ForeName>Sahl Khalid</ForeName>
<Initials>SK</Initials>
<AffiliationInfo><Affiliation>Department of Clinical Neurosciences, Karolinska Institutet, Stockholm, Sweden.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Hillert</LastName>
<ForeName>Jan</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Department of Clinical Neurosciences, Karolinska Institutet, Stockholm, Sweden.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Matute</LastName>
<ForeName>Carlos</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>CIBERNED, Achucarro Basque Center for Neuroscience, and Departamento de Neurociencias, Universidad del País Vasco, Leioa, Spain and.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Antiguedad</LastName>
<ForeName>Alfredo</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>Servicio de Neurología, Hospital Universitario Basurto-Osakidetza, Bilbao, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><CollectiveName>ANZgene Consortium</CollectiveName>
</Author>
<Author ValidYN="Y"><LastName>Wiley</LastName>
<ForeName>James S</ForeName>
<Initials>JS</Initials>
<AffiliationInfo><Affiliation>Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia, james.wiley@florey.edu.au.</Affiliation>
</AffiliationInfo>
</Author>
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<PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType>
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<Month>07</Month>
<Day>17</Day>
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<ISSNLinking>0964-6906</ISSNLinking>
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</MeshHeading>
<MeshHeading><DescriptorName UI="D001120" MajorTopicYN="N">Arginine</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D044362" MajorTopicYN="N" Type="Geographic">Australasia</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D001665" MajorTopicYN="N">Binding Sites</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D044465" MajorTopicYN="N">European Continental Ancestry Group</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D056726" MajorTopicYN="N">Genetic Association Studies</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D020022" MajorTopicYN="N">Genetic Predisposition to Disease</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D005973" MajorTopicYN="N">Glutamine</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008958" MajorTopicYN="N">Models, Molecular</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D009103" MajorTopicYN="N">Multiple Sclerosis</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
<QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D058486" MajorTopicYN="N">Receptors, Purinergic P2X7</DescriptorName>
<QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName>
<QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
</MeshHeadingList>
<InvestigatorList><Investigator ValidYN="Y"><LastName>Baxter</LastName>
<ForeName>Alan G</ForeName>
<Initials>AG</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Kermode</LastName>
<ForeName>Allan G</ForeName>
<Initials>AG</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Taylor</LastName>
<ForeName>Bruce V</ForeName>
<Initials>BV</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Booth</LastName>
<ForeName>David R</ForeName>
<Initials>DR</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Mason</LastName>
<ForeName>Deborah F</ForeName>
<Initials>DF</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Stewart</LastName>
<ForeName>Graeme J</ForeName>
<Initials>GJ</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Butzkueven</LastName>
<ForeName>Helmut</ForeName>
<Initials>H</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Charlesworth</LastName>
<ForeName>Jac C</ForeName>
<Initials>JC</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Wiley</LastName>
<ForeName>James S</ForeName>
<Initials>JS</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Lechner-Scott</LastName>
<ForeName>Jeannette S</ForeName>
<Initials>JS</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Field</LastName>
<ForeName>Judith</ForeName>
<Initials>J</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Tajouri</LastName>
<ForeName>Lotti</ForeName>
<Initials>L</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Griffiths</LastName>
<ForeName>Lyn R</ForeName>
<Initials>LR</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Slee</LastName>
<ForeName>Mark</ForeName>
<Initials>M</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Brown</LastName>
<ForeName>Matthew A</ForeName>
<Initials>MA</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Moscato</LastName>
<ForeName>Pablo</ForeName>
<Initials>P</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Scott</LastName>
<ForeName>Rodney J</ForeName>
<Initials>RJ</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Broadley</LastName>
<ForeName>Simon A</ForeName>
<Initials>SA</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Vucic</LastName>
<ForeName>Steve</ForeName>
<Initials>S</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Kilpatrick</LastName>
<ForeName>Trevor J</ForeName>
<Initials>TJ</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Carroll</LastName>
<ForeName>William M</ForeName>
<Initials>WM</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Barnett</LastName>
<ForeName>Michael H</ForeName>
<Initials>MH</Initials>
</Investigator>
</InvestigatorList>
</MedlineCitation>
<PubmedData><History><PubMedPubDate PubStatus="received"><Year>2015</Year>
<Month>05</Month>
<Day>13</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="accepted"><Year>2015</Year>
<Month>07</Month>
<Day>10</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="entrez"><Year>2015</Year>
<Month>7</Month>
<Day>19</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="pubmed"><Year>2015</Year>
<Month>7</Month>
<Day>19</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="medline"><Year>2016</Year>
<Month>7</Month>
<Day>7</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
</History>
<PublicationStatus>ppublish</PublicationStatus>
<ArticleIdList><ArticleId IdType="pubmed">26188005</ArticleId>
<ArticleId IdType="pii">ddv278</ArticleId>
<ArticleId IdType="doi">10.1093/hmg/ddv278</ArticleId>
</ArticleIdList>
</PubmedData>
</pubmed>
<affiliations><list><country><li>Allemagne</li>
<li>Australie</li>
<li>Espagne</li>
<li>France</li>
<li>Royaume-Uni</li>
<li>Suède</li>
</country>
<region><li>Languedoc-Roussillon</li>
<li>Occitanie (région administrative)</li>
<li>Svealand</li>
<li>Victoria (État)</li>
</region>
<settlement><li>Melbourne</li>
<li>Montpellier</li>
<li>Stockholm</li>
</settlement>
<orgName><li>Université de Melbourne</li>
</orgName>
</list>
<tree><noCountry><name sortKey="Matute, Carlos" sort="Matute, Carlos" uniqKey="Matute C" first="Carlos" last="Matute">Carlos Matute</name>
</noCountry>
<country name="Australie"><region name="Victoria (État)"><name sortKey="Gu, Ben J" sort="Gu, Ben J" uniqKey="Gu B" first="Ben J" last="Gu">Ben J. Gu</name>
</region>
<name sortKey="Butzkueven, Helmut" sort="Butzkueven, Helmut" uniqKey="Butzkueven H" first="Helmut" last="Butzkueven">Helmut Butzkueven</name>
<name sortKey="Field, Judith" sort="Field, Judith" uniqKey="Field J" first="Judith" last="Field">Judith Field</name>
<name sortKey="Gresle, Melissa" sort="Gresle, Melissa" uniqKey="Gresle M" first="Melissa" last="Gresle">Melissa Gresle</name>
<name sortKey="Kilpatrick, Trevor J" sort="Kilpatrick, Trevor J" uniqKey="Kilpatrick T" first="Trevor J" last="Kilpatrick">Trevor J. Kilpatrick</name>
<name sortKey="Laws, Simon M" sort="Laws, Simon M" uniqKey="Laws S" first="Simon M" last="Laws">Simon M. Laws</name>
<name sortKey="Lea, Rodney" sort="Lea, Rodney" uniqKey="Lea R" first="Rodney" last="Lea">Rodney Lea</name>
<name sortKey="Lechner Scott, Jeannette" sort="Lechner Scott, Jeannette" uniqKey="Lechner Scott J" first="Jeannette" last="Lechner-Scott">Jeannette Lechner-Scott</name>
<name sortKey="Ou, Amber" sort="Ou, Amber" uniqKey="Ou A" first="Amber" last="Ou">Amber Ou</name>
<name sortKey="Petrou, Steven" sort="Petrou, Steven" uniqKey="Petrou S" first="Steven" last="Petrou">Steven Petrou</name>
<name sortKey="Scott, Rodney" sort="Scott, Rodney" uniqKey="Scott R" first="Rodney" last="Scott">Rodney Scott</name>
<name sortKey="Stankovich, Jim" sort="Stankovich, Jim" uniqKey="Stankovich J" first="Jim" last="Stankovich">Jim Stankovich</name>
<name sortKey="Taylor, Bruce V" sort="Taylor, Bruce V" uniqKey="Taylor B" first="Bruce V" last="Taylor">Bruce V. Taylor</name>
<name sortKey="Wiley, James S" sort="Wiley, James S" uniqKey="Wiley J" first="James S" last="Wiley">James S. Wiley</name>
</country>
<country name="France"><region name="Occitanie (région administrative)"><name sortKey="Dutertre, Sebastien" sort="Dutertre, Sebastien" uniqKey="Dutertre S" first="Sébastien" last="Dutertre">Sébastien Dutertre</name>
</region>
</country>
<country name="Allemagne"><noRegion><name sortKey="Hoffjan, Sabine" sort="Hoffjan, Sabine" uniqKey="Hoffjan S" first="Sabine" last="Hoffjan">Sabine Hoffjan</name>
</noRegion>
<name sortKey="Akkad, Denis A" sort="Akkad, Denis A" uniqKey="Akkad D" first="Denis A" last="Akkad">Denis A. Akkad</name>
</country>
<country name="Royaume-Uni"><noRegion><name sortKey="Graham, Colin A" sort="Graham, Colin A" uniqKey="Graham C" first="Colin A" last="Graham">Colin A. Graham</name>
</noRegion>
<name sortKey="Hawkins, Stanley" sort="Hawkins, Stanley" uniqKey="Hawkins S" first="Stanley" last="Hawkins">Stanley Hawkins</name>
</country>
<country name="Suède"><region name="Svealand"><name sortKey="Glaser, Anna" sort="Glaser, Anna" uniqKey="Glaser A" first="Anna" last="Glaser">Anna Glaser</name>
</region>
<name sortKey="Bedri, Sahl Khalid" sort="Bedri, Sahl Khalid" uniqKey="Bedri S" first="Sahl Khalid" last="Bedri">Sahl Khalid Bedri</name>
<name sortKey="Hillert, Jan" sort="Hillert, Jan" uniqKey="Hillert J" first="Jan" last="Hillert">Jan Hillert</name>
</country>
<country name="Espagne"><noRegion><name sortKey="Antiguedad, Alfredo" sort="Antiguedad, Alfredo" uniqKey="Antiguedad A" first="Alfredo" last="Antiguedad">Alfredo Antiguedad</name>
</noRegion>
</country>
</tree>
</affiliations>
</record>

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   |wiki=    Wicri/Asie
   |area=    AustralieFrV1
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   |type=    RBID
   |clé=     pubmed:26188005
   |texte=   A rare P2X7 variant Arg307Gln with absent pore formation function protects against neuroinflammation in multiple sclerosis.
}}

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	Serveur d'exploration sur les relations entre la France et l'Australie
	Attention, ce site est en cours de développement ! Attention, site généré par des moyens informatiques à partir de corpus bruts. Les informations ne sont donc pas validées.

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A rare P2X7 variant Arg307Gln with absent pore formation function protects against neuroinflammation in multiple sclerosis.

A rare P2X7 variant Arg307Gln with absent pore formation function protects against neuroinflammation in multiple sclerosis.

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