MovDisordV3, France, Analysis, bibRecord, 000129

Association between Parkinson's Disease and the HLA-DRB1 Locus

Identifieur interne : 000129 ( France/Analysis ); précédent : 000128; suivant : 000130

Association between Parkinson's Disease and the HLA-DRB1 Locus

Auteurs : Ismail Ahmed [France] ; Ryad Tamouza [France] ; Marc Delord [France] ; Rajagopal Krishnamoorthy [France] ; Christophe Tzourio [France] ; Claire Mulot [France] ; Magali Nacfer [France] ; Jean-Charles Lambert [France] ; Philippe Beaune [France] ; Pierre Laurent-Puig [France] ; Marie-Anne Loriot [France] ; Dominique Charron [France] ; Alexis Elbaz [France]

Source :

Movement disorders [ 0885-3185 ] ; 2012.

RBID : Pascal:12-0340017

Descripteurs français

Pascal (Inist)
- Maladie de Parkinson, Pathologie du système nerveux, Système HLA, Locus, Système histocompatibilité majeur.
Wicri :
- geographic : France.

English descriptors

KwdEn :
- Adult, Aged, Aged, 80 and over, DNA (genetics), Female, France (epidemiology), Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, HLA-DRB1 Chains (genetics), HLA-System, Haplotypes, Humans, Locus, Major histocompatibility system, Male, Middle Aged, Nervous system diseases, Parkinson Disease (epidemiology), Parkinson Disease (genetics), Parkinson disease, Polymorphism, Single Nucleotide, Socioeconomic Factors.
MESH :
- chemical , genetics : DNA, HLA-DRB1 Chains.
- geographic , epidemiology : France.
- epidemiology : Parkinson Disease.
- genetics : Parkinson Disease.
- Adult, Aged, Aged, 80 and over, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Haplotypes, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Socioeconomic Factors.

Abstract

Two genome-wide association studies (GWASs) recently highlighted the HLA-DRA and HLA-DRB5 genes as associated with Parkinson disease (PD). However, because HLA-DRA displays a low level of polymorphisms and HLA-DRB5 is only present in approximately 20% of the population, these findings are difficult to interpret. Our aims were: (1) to replicate and investigate in greater detail the association between PD and the HLA-DR region; (2) to identify PD-associated HLA alleles; and (3) to perform a meta-analysis of our top finding. As part of 2 French population-based case-control studies of PD including highly ethnically homogeneous participants, we investigated the association between PD and 51 Single-nucleotide polymorphisms (SNPs) in the HLA-DR region. HLA-DRB1 alleles were imputed using the HLA*IMP software. HLA typing was performed in a subsample of the participants. We performed a meta-analysis of our top finding based on 4 GWAS data sets. Among 499 cases and 1123 controls, after correction for multiple testing, we found an association with rs660895 (OR/minor allele, 0.70; 95% CI, 0.57-0.87) within the HLA-DRB1 gene, which encodes the most polymorphic HLA-DR chain (DRβ). A meta-analysis (7996 cases, 36455 controls) confirmed this association (OR, 0.86; 95% CI, 0.82-0.91; P < .0001). SNP-based imputation of HLA alleles showed an inverse association between PD and the HLA-DRB1^*04 allele. We replicated an association between PD and the HLA-DR region and provided further insight into the loci and alleles involved. The highly polymorphic HLA-DRB1 locus contains rs660895, which represents a more legitimate candidate than previous ones. Our finding is in agreement with the hypothesis of an immune component in PD pathophysiology.

Url:

http://www.hal.inserm.fr/inserm-00721562

Affiliations:

Links to Exploration step

Pascal:12-0340017

Le document en format XML

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<placeName><settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Lambert, Jean Charles" sort="Lambert, Jean Charles" uniqKey="Lambert J" first="Jean-Charles" last="Lambert">Jean-Charles Lambert</name>
<affiliation wicri:level="1"><inist:fA14 i1="08"><s1>INSERM, U744, Pasteur Institute from Lille, University of Lille-Nord de France</s1>
<s2>Lille</s2>
<s3>FRA</s3>
<sZ>8 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName><settlement type="city">Lille</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Beaune, Philippe" sort="Beaune, Philippe" uniqKey="Beaune P" first="Philippe" last="Beaune">Philippe Beaune</name>
<affiliation wicri:level="4"><inist:fA14 i1="06"><s1>Université Paris Descartes, INSERM UMR-S 775</s1>
<s2>Paris</s2>
<s3>FRA</s3>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName><settlement type="city">Paris</settlement>
</placeName>
<orgName type="university">Université Paris Descartes</orgName>
<placeName><settlement type="city">Paris</settlement>
<region type="region" nuts="2">Île-de-France</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="09"><s1>Assistance Publique Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Service de Biochimie, Unité Fonctionnelle de Pharmacogénétique et Oncologie Moléculaire</s1>
<s2>Paris</s2>
<s3>FRA</s3>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName><settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Laurent Puig, Pierre" sort="Laurent Puig, Pierre" uniqKey="Laurent Puig P" first="Pierre" last="Laurent-Puig">Pierre Laurent-Puig</name>
<affiliation wicri:level="4"><inist:fA14 i1="06"><s1>Université Paris Descartes, INSERM UMR-S 775</s1>
<s2>Paris</s2>
<s3>FRA</s3>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName><settlement type="city">Paris</settlement>
</placeName>
<orgName type="university">Université Paris Descartes</orgName>
<placeName><settlement type="city">Paris</settlement>
<region type="region" nuts="2">Île-de-France</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="09"><s1>Assistance Publique Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Service de Biochimie, Unité Fonctionnelle de Pharmacogénétique et Oncologie Moléculaire</s1>
<s2>Paris</s2>
<s3>FRA</s3>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName><settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Loriot, Marie Anne" sort="Loriot, Marie Anne" uniqKey="Loriot M" first="Marie-Anne" last="Loriot">Marie-Anne Loriot</name>
<affiliation wicri:level="4"><inist:fA14 i1="06"><s1>Université Paris Descartes, INSERM UMR-S 775</s1>
<s2>Paris</s2>
<s3>FRA</s3>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName><settlement type="city">Paris</settlement>
</placeName>
<orgName type="university">Université Paris Descartes</orgName>
<placeName><settlement type="city">Paris</settlement>
<region type="region" nuts="2">Île-de-France</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="09"><s1>Assistance Publique Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Service de Biochimie, Unité Fonctionnelle de Pharmacogénétique et Oncologie Moléculaire</s1>
<s2>Paris</s2>
<s3>FRA</s3>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName><settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Charron, Dominique" sort="Charron, Dominique" uniqKey="Charron D" first="Dominique" last="Charron">Dominique Charron</name>
<affiliation wicri:level="1"><inist:fA14 i1="03"><s1>INSERM, U940, and Laboratoire Jean Dausset, Hôpital Saint Louis</s1>
<s2>Paris</s2>
<s3>FRA</s3>
<sZ>2 aut.</sZ>
<sZ>12 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName><settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Elbaz, Alexis" sort="Elbaz, Alexis" uniqKey="Elbaz A" first="Alexis" last="Elbaz">Alexis Elbaz</name>
<affiliation wicri:level="1"><inist:fA14 i1="02"><s1>UPMC Univ Paris 06, UMR_S708, Neuroepidemiology</s1>
<s2>Paris</s2>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>13 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName><settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j" type="main">Movement disorders</title>
<title level="j" type="abbreviated">Mov. disord.</title>
<idno type="ISSN">0885-3185</idno>
<imprint><date when="2012">2012</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><title level="j" type="main">Movement disorders</title>
<title level="j" type="abbreviated">Mov. disord.</title>
<idno type="ISSN">0885-3185</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term>
<term>Aged</term>
<term>Aged, 80 and over</term>
<term>DNA (genetics)</term>
<term>Female</term>
<term>France (epidemiology)</term>
<term>Genetic Predisposition to Disease</term>
<term>Genome-Wide Association Study</term>
<term>Genotype</term>
<term>HLA-DRB1 Chains (genetics)</term>
<term>HLA-System</term>
<term>Haplotypes</term>
<term>Humans</term>
<term>Locus</term>
<term>Major histocompatibility system</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Nervous system diseases</term>
<term>Parkinson Disease (epidemiology)</term>
<term>Parkinson Disease (genetics)</term>
<term>Parkinson disease</term>
<term>Polymorphism, Single Nucleotide</term>
<term>Socioeconomic Factors</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>DNA</term>
<term>HLA-DRB1 Chains</term>
</keywords>
<keywords scheme="MESH" type="geographic" qualifier="epidemiology" xml:lang="en"><term>France</term>
</keywords>
<keywords scheme="MESH" qualifier="epidemiology" xml:lang="en"><term>Parkinson Disease</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Parkinson Disease</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Adult</term>
<term>Aged</term>
<term>Aged, 80 and over</term>
<term>Female</term>
<term>Genetic Predisposition to Disease</term>
<term>Genome-Wide Association Study</term>
<term>Genotype</term>
<term>Haplotypes</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Polymorphism, Single Nucleotide</term>
<term>Socioeconomic Factors</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Maladie de Parkinson</term>
<term>Pathologie du   système nerveux</term>
<term>Système HLA</term>
<term>Locus</term>
<term>Système histocompatibilité majeur</term>
</keywords>
<keywords scheme="Wicri" type="geographic" xml:lang="fr"><term>France</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Two genome-wide association studies (GWASs) recently highlighted the HLA-DRA and HLA-DRB5 genes as associated with Parkinson disease (PD). However, because HLA-DRA displays a low level of polymorphisms and HLA-DRB5 is only present in approximately 20% of the population, these findings are difficult to interpret. Our aims were: (1) to replicate and investigate in greater detail the association between PD and the HLA-DR region; (2) to identify PD-associated HLA alleles; and (3) to perform a meta-analysis of our top finding. As part of 2 French population-based case-control studies of PD including highly ethnically homogeneous participants, we investigated the association between PD and 51 Single-nucleotide polymorphisms (SNPs) in the HLA-DR region. HLA-DRB1 alleles were imputed using the HLA*IMP software. HLA typing was performed in a subsample of the participants. We performed a meta-analysis of our top finding based on 4 GWAS data sets. Among 499 cases and 1123 controls, after correction for multiple testing, we found an association with rs660895 (OR/minor allele, 0.70; 95% CI, 0.57-0.87) within the HLA-DRB1 gene, which encodes the most polymorphic HLA-DR chain (DRβ). A meta-analysis (7996 cases, 36455 controls) confirmed this association (OR, 0.86; 95% CI, 0.82-0.91; P < .0001). SNP-based imputation of HLA alleles showed an inverse association between PD and the HLA-DRB1<sup>*</sup>
04 allele. We replicated an association between PD and the HLA-DR region and provided further insight into the loci and alleles involved. The highly polymorphic HLA-DRB1 locus contains rs660895, which represents a more legitimate candidate than previous ones. Our finding is in agreement with the hypothesis of an immune component in PD pathophysiology.</div>
</front>
</TEI>
<affiliations><list><country><li>France</li>
</country>
<region><li>Île-de-France</li>
</region>
<settlement><li>Lille</li>
<li>Paris</li>
</settlement>
<orgName><li>Université Paris Descartes</li>
</orgName>
</list>
<tree><country name="France"><noRegion><name sortKey="Ahmed, Ismail" sort="Ahmed, Ismail" uniqKey="Ahmed I" first="Ismail" last="Ahmed">Ismail Ahmed</name>
</noRegion>
<name sortKey="Ahmed, Ismail" sort="Ahmed, Ismail" uniqKey="Ahmed I" first="Ismail" last="Ahmed">Ismail Ahmed</name>
<name sortKey="Beaune, Philippe" sort="Beaune, Philippe" uniqKey="Beaune P" first="Philippe" last="Beaune">Philippe Beaune</name>
<name sortKey="Beaune, Philippe" sort="Beaune, Philippe" uniqKey="Beaune P" first="Philippe" last="Beaune">Philippe Beaune</name>
<name sortKey="Charron, Dominique" sort="Charron, Dominique" uniqKey="Charron D" first="Dominique" last="Charron">Dominique Charron</name>
<name sortKey="Delord, Marc" sort="Delord, Marc" uniqKey="Delord M" first="Marc" last="Delord">Marc Delord</name>
<name sortKey="Elbaz, Alexis" sort="Elbaz, Alexis" uniqKey="Elbaz A" first="Alexis" last="Elbaz">Alexis Elbaz</name>
<name sortKey="Krishnamoorthy, Rajagopal" sort="Krishnamoorthy, Rajagopal" uniqKey="Krishnamoorthy R" first="Rajagopal" last="Krishnamoorthy">Rajagopal Krishnamoorthy</name>
<name sortKey="Lambert, Jean Charles" sort="Lambert, Jean Charles" uniqKey="Lambert J" first="Jean-Charles" last="Lambert">Jean-Charles Lambert</name>
<name sortKey="Laurent Puig, Pierre" sort="Laurent Puig, Pierre" uniqKey="Laurent Puig P" first="Pierre" last="Laurent-Puig">Pierre Laurent-Puig</name>
<name sortKey="Laurent Puig, Pierre" sort="Laurent Puig, Pierre" uniqKey="Laurent Puig P" first="Pierre" last="Laurent-Puig">Pierre Laurent-Puig</name>
<name sortKey="Loriot, Marie Anne" sort="Loriot, Marie Anne" uniqKey="Loriot M" first="Marie-Anne" last="Loriot">Marie-Anne Loriot</name>
<name sortKey="Loriot, Marie Anne" sort="Loriot, Marie Anne" uniqKey="Loriot M" first="Marie-Anne" last="Loriot">Marie-Anne Loriot</name>
<name sortKey="Mulot, Claire" sort="Mulot, Claire" uniqKey="Mulot C" first="Claire" last="Mulot">Claire Mulot</name>
<name sortKey="Mulot, Claire" sort="Mulot, Claire" uniqKey="Mulot C" first="Claire" last="Mulot">Claire Mulot</name>
<name sortKey="Nacfer, Magali" sort="Nacfer, Magali" uniqKey="Nacfer M" first="Magali" last="Nacfer">Magali Nacfer</name>
<name sortKey="Nacfer, Magali" sort="Nacfer, Magali" uniqKey="Nacfer M" first="Magali" last="Nacfer">Magali Nacfer</name>
<name sortKey="Tamouza, Ryad" sort="Tamouza, Ryad" uniqKey="Tamouza R" first="Ryad" last="Tamouza">Ryad Tamouza</name>
<name sortKey="Tzourio, Christophe" sort="Tzourio, Christophe" uniqKey="Tzourio C" first="Christophe" last="Tzourio">Christophe Tzourio</name>
<name sortKey="Tzourio, Christophe" sort="Tzourio, Christophe" uniqKey="Tzourio C" first="Christophe" last="Tzourio">Christophe Tzourio</name>
</country>
</tree>
</affiliations>
</record>

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Movement Disorders (revue)

Association between Parkinson's Disease and the HLA-DRB1 Locus

Association between Parkinson's Disease and the HLA-DRB1 Locus

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	Movement Disorders (revue)
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