ParkinsonFranceV1, Main, Merge, bibRecord, 003482

Association between Parkinson's disease and polymorphisms in the nNOS and iNOS genes in a community-based case-control study.

Identifieur interne : 003482 ( Main/Merge ); précédent : 003481; suivant : 003483

Association between Parkinson's disease and polymorphisms in the nNOS and iNOS genes in a community-based case-control study.

Auteurs : Clotilde Levecque [France] ; Alexis Elbaz [France] ; Jacqueline Clavel [France] ; Florence Richard [France] ; Jean-Sébastien Vidal [France] ; Philippe Amouyel [France] ; Christophe Tzourio [France] ; Annick Alpérovitch [France] ; Marie-Christine Chartier-Harlin [France]

Source :

Human Molecular Genetics [ 0964-6906 ] ; 2003-01-01.

RBID : Hal:inserm-00266834

Abstract

Excess of nitric oxide (NO) has been shown to exert neurotoxic impacts in the brain. Moreover, inhibition of two NO-synthesizing enzymes, neuronal NOS (nNOS) and inducible NOS (iNOS), displays neuroprotective effects in the MPTP model of Parkinson's disease (PD). These data suggest a possible involvement of NOS as factors controlling the resistance of the nigral dopaminergic neurons to environmental insults. Therefore, we investigated whether polymorphisms present in these genes could contribute to the risk of developing PD. We carried out a community-based case-control study among subjects enrolled in the Mutualit?ociale Agricole, the French health insurance organization for workers connected to agriculture. Two-hundred and nine PD patients and 488 controls of European (mostly French) ancestry and matched for age, sex and region of residency were included in this study. Associations were observed with polymorphisms present in exon 22 of iNOS (OR for AA carriers=0.50, 95% CI=0.29-0.86, P=0.01) and in exon 29 of nNOS (OR for carriers of the T allele=1.53, 95% CI=1.08-2.16, P=0.02); no association was observed with a polymorphism in exon 18 of nNOS (OR for carriers of the T allele=1.20, 95% CI=0.85-1.69, P=0.30). Moreover, a significant interaction of the nNOS polymorphisms with current and ever cigarette smoking was found (nNOS 18, P=0.05; nNOS 29, P=0.04). All together, these data favour an involvement of these two genes as new modifier genes in PD.

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<author><name sortKey="Richard, Florence" sort="Richard, Florence" uniqKey="Richard F" first="Florence" last="Richard">Florence Richard</name>
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<author><name sortKey="Vidal, Jean Sebastien" sort="Vidal, Jean Sebastien" uniqKey="Vidal J" first="Jean-Sébastien" last="Vidal">Jean-Sébastien Vidal</name>
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<author><name sortKey="Amouyel, Philippe" sort="Amouyel, Philippe" uniqKey="Amouyel P" first="Philippe" last="Amouyel">Philippe Amouyel</name>
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<author><name sortKey="Tzourio, Christophe" sort="Tzourio, Christophe" uniqKey="Tzourio C" first="Christophe" last="Tzourio">Christophe Tzourio</name>
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<author><name sortKey="Alperovitch, Annick" sort="Alperovitch, Annick" uniqKey="Alperovitch A" first="Annick" last="Alpérovitch">Annick Alpérovitch</name>
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<author><name sortKey="Chartier Harlin, Marie Christine" sort="Chartier Harlin, Marie Christine" uniqKey="Chartier Harlin M" first="Marie-Christine" last="Chartier-Harlin">Marie-Christine Chartier-Harlin</name>
<affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-18640" status="OLD">  <orgName>Epidémiologie des maladies chroniques: impact des intéractions gène environnement sur la santé des populations</orgName>
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  <orgName type="acronym">INSERM</orgName>
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  <orgName type="acronym">CHRU Lille</orgName>
  <desc>    <address>      <addrLine>2, avenue Oscar Lambret - 59037 Lille Cedex</addrLine>
      <country key="FR"></country>
    </address>
    <ref type="url">http://www.chru-lille.fr/</ref>
  </desc>
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<tutelle active="#struct-300166" type="direct"><org type="institution" xml:id="struct-300166" status="VALID">  <orgName>Institut Pasteur de Lille</orgName>
  <desc>    <address>      <country key="FR"></country>
    </address>
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  <orgName>Université de Lille, Droit et Santé</orgName>
  <desc>    <address>      <addrLine>42 rue Paul Duez 59000 Lille</addrLine>
      <country key="FR"></country>
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    <ref type="url">http://www.univ-lille2.fr/</ref>
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<country>France</country>
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<series><title level="j">Human Molecular Genetics</title>
<idno type="ISSN">0964-6906</idno>
<imprint><date type="datePub">2003-01-01</date>
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<front><div type="abstract" xml:lang="en">Excess of nitric oxide (NO) has been shown to exert neurotoxic impacts in the brain. Moreover, inhibition of two NO-synthesizing enzymes, neuronal NOS (nNOS) and inducible NOS (iNOS), displays neuroprotective effects in the MPTP model of Parkinson's disease (PD). These data suggest a possible involvement of NOS as factors controlling the resistance of the nigral dopaminergic neurons to environmental insults. Therefore, we investigated whether polymorphisms present in these genes could contribute to the risk of developing PD. We carried out a community-based case-control study among subjects enrolled in the Mutualit?ociale Agricole, the French health insurance organization for workers connected to agriculture. Two-hundred and nine PD patients and 488 controls of European (mostly French) ancestry and matched for age, sex and region of residency were included in this study. Associations were observed with polymorphisms present in exon 22 of iNOS (OR for AA carriers=0.50, 95% CI=0.29-0.86, P=0.01) and in exon 29 of nNOS (OR for carriers of the T allele=1.53, 95% CI=1.08-2.16, P=0.02); no association was observed with a polymorphism in exon 18 of nNOS (OR for carriers of the T allele=1.20, 95% CI=0.85-1.69, P=0.30). Moreover, a significant interaction of the nNOS polymorphisms with current and ever cigarette smoking was found (nNOS 18, P=0.05; nNOS 29, P=0.04). All together, these data favour an involvement of these two genes as new modifier genes in PD.</div>
</front>
</TEI>
</record>

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	La maladie de Parkinson en France (serveur d'exploration)
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La maladie de Parkinson en France (serveur d'exploration)

Association between Parkinson's disease and polymorphisms in the nNOS and iNOS genes in a community-based case-control study.

Association between Parkinson's disease and polymorphisms in the nNOS and iNOS genes in a community-based case-control study.

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