La maladie de Parkinson au Canada (serveur d'exploration)

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A Multicenter Study of Glucocerebrosidase Mutations in Dementia With Lewy Bodies

Identifieur interne : 000E72 ( Main/Exploration ); précédent : 000E71; suivant : 000E73

A Multicenter Study of Glucocerebrosidase Mutations in Dementia With Lewy Bodies

Auteurs : Michael A. Nalls ; Raquel Duran ; Grisel Lopez ; Marzena Kurzawa-Akanbi ; Ian G. Mckeith ; Patrick F. Chinnery ; Christopher M. Morris ; Jessie Theuns ; David Crosiers ; Patrick Cras ; Sebastiaan Engelborghs ; Peter Paul De Deyn ; Christine Van Broeckhoven ; David M. A. Mann ; Julie Snowden ; Stuart Pickering-Brown ; Nicola Halliwell ; Yvonne Davidson ; Linda Gibbons ; Jenny Harris ; Una-Marie Sheerin ; Jose Bras ; John Hardy ; Lorraine Clark ; Karen Marder ; Lawrence S. Honig ; Daniela Berg ; Walter Maetzler ; Kathrin Brockmann ; Thomas Gasser ; Fabiana Novellino ; Aldo Quattrone ; Grazia Annesi ; Elvira Valeria De Marco ; Ekaterina Rogaeva ; Mario Masellis ; Sandra E. Black ; Juan M. Bilbao ; Tatiana Foroud ; Bernardino Ghetti ; William C. Nichols ; Nathan Pankratz ; Glenda Halliday ; Suzanne Lesage ; Stephan Klebe ; Alexandra Durr ; Charles Duyckaerts ; Alexis Brice ; Benoit I. Giasson ; John Q. Trojanowski ; Howard I. Hurtig ; Nahid Tayebi ; Claudia Landazabal ; Melanie A. Knight ; Margaux Keller ; Andrew B. Singleton ; Tyra G. Wolfsberg ; Ellen Sidransky

Source :

RBID : PMC:3841974

English descriptors

Abstract

Importance

While mutations in glucocerebrosidase (GBA1) are associated with an increased risk for Parkinson disease (PD), it is important to establish whether such mutations are also a common risk factor for other Lewy body disorders.

Objective

To establish whether GBA1 mutations are a risk factor for dementia with Lewy bodies (DLB).

Design

We compared genotype data on patients and controls from 11 centers. Data concerning demographics, age at onset, disease duration, and clinical and pathological features were collected when available. We conducted pooled analyses using logistic regression to investigate GBA1 mutation carrier status as predicting DLB or PD with dementia status, using common control subjects as a reference group. Random-effects meta-analyses were conducted to account for additional heterogeneity.

Setting

Eleven centers from sites around the world performing genotyping.

Participants

Seven hundred twenty-one cases met diagnostic criteria for DLB and 151 had PD with dementia. We compared these cases with 1962 controls from the same centers matched for age, sex, and ethnicity.

Main Outcome Measures

Frequency of GBA1 mutations in cases and controls.

Results

We found a significant association between GBA1 mutation carrier status and DLB, with an odds ratio of 8.28 (95% CI, 4.78–14.88). The odds ratio for PD with dementia was 6.48 (95% CI, 2.53–15.37). The mean age at diagnosis of DLB was earlier in GBA1 mutation carriers than in noncarriers (63.5 vs 68.9 years; P<.001), with higher disease severity scores.

Conclusions and Relevance

Mutations in GBA1 are a significant risk factor for DLB. GBA1 mutations likely play an even larger role in the genetic etiology of DLB than in PD, providing insight into the role of glucocerebrosidase in Lewy body disease.


Url:
DOI: 10.1001/jamaneurol.2013.1925
PubMed: 23588557
PubMed Central: 3841974


Affiliations:


Links toward previous steps (curation, corpus...)


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<title xml:lang="en" level="a" type="main">A Multicenter Study of Glucocerebrosidase Mutations in Dementia With Lewy Bodies</title>
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<name sortKey="Nalls, Michael A" sort="Nalls, Michael A" uniqKey="Nalls M" first="Michael A." last="Nalls">Michael A. Nalls</name>
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<name sortKey="Duran, Raquel" sort="Duran, Raquel" uniqKey="Duran R" first="Raquel" last="Duran">Raquel Duran</name>
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<name sortKey="Lopez, Grisel" sort="Lopez, Grisel" uniqKey="Lopez G" first="Grisel" last="Lopez">Grisel Lopez</name>
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<name sortKey="Kurzawa Akanbi, Marzena" sort="Kurzawa Akanbi, Marzena" uniqKey="Kurzawa Akanbi M" first="Marzena" last="Kurzawa-Akanbi">Marzena Kurzawa-Akanbi</name>
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<name sortKey="Engelborghs, Sebastiaan" sort="Engelborghs, Sebastiaan" uniqKey="Engelborghs S" first="Sebastiaan" last="Engelborghs">Sebastiaan Engelborghs</name>
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<name sortKey="Lesage, Suzanne" sort="Lesage, Suzanne" uniqKey="Lesage S" first="Suzanne" last="Lesage">Suzanne Lesage</name>
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</author>
<author>
<name sortKey="Duyckaerts, Charles" sort="Duyckaerts, Charles" uniqKey="Duyckaerts C" first="Charles" last="Duyckaerts">Charles Duyckaerts</name>
</author>
<author>
<name sortKey="Brice, Alexis" sort="Brice, Alexis" uniqKey="Brice A" first="Alexis" last="Brice">Alexis Brice</name>
</author>
<author>
<name sortKey="Giasson, Benoit I" sort="Giasson, Benoit I" uniqKey="Giasson B" first="Benoit I." last="Giasson">Benoit I. Giasson</name>
</author>
<author>
<name sortKey="Trojanowski, John Q" sort="Trojanowski, John Q" uniqKey="Trojanowski J" first="John Q." last="Trojanowski">John Q. Trojanowski</name>
</author>
<author>
<name sortKey="Hurtig, Howard I" sort="Hurtig, Howard I" uniqKey="Hurtig H" first="Howard I." last="Hurtig">Howard I. Hurtig</name>
</author>
<author>
<name sortKey="Tayebi, Nahid" sort="Tayebi, Nahid" uniqKey="Tayebi N" first="Nahid" last="Tayebi">Nahid Tayebi</name>
</author>
<author>
<name sortKey="Landazabal, Claudia" sort="Landazabal, Claudia" uniqKey="Landazabal C" first="Claudia" last="Landazabal">Claudia Landazabal</name>
</author>
<author>
<name sortKey="Knight, Melanie A" sort="Knight, Melanie A" uniqKey="Knight M" first="Melanie A." last="Knight">Melanie A. Knight</name>
</author>
<author>
<name sortKey="Keller, Margaux" sort="Keller, Margaux" uniqKey="Keller M" first="Margaux" last="Keller">Margaux Keller</name>
</author>
<author>
<name sortKey="Singleton, Andrew B" sort="Singleton, Andrew B" uniqKey="Singleton A" first="Andrew B." last="Singleton">Andrew B. Singleton</name>
</author>
<author>
<name sortKey="Wolfsberg, Tyra G" sort="Wolfsberg, Tyra G" uniqKey="Wolfsberg T" first="Tyra G." last="Wolfsberg">Tyra G. Wolfsberg</name>
</author>
<author>
<name sortKey="Sidransky, Ellen" sort="Sidransky, Ellen" uniqKey="Sidransky E" first="Ellen" last="Sidransky">Ellen Sidransky</name>
</author>
</analytic>
<series>
<title level="j">JAMA neurology</title>
<idno type="ISSN">2168-6149</idno>
<idno type="eISSN">2168-6157</idno>
<imprint>
<date when="2013">2013</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass>
<keywords scheme="KwdEn" xml:lang="en">
<term>Aged</term>
<term>Aged, 80 and over</term>
<term>Case-Control Studies</term>
<term>Female</term>
<term>Genetic Association Studies (methods)</term>
<term>Genotype</term>
<term>Glucosylceramidase (genetics)</term>
<term>Humans</term>
<term>Lewy Body Disease (diagnosis)</term>
<term>Lewy Body Disease (epidemiology)</term>
<term>Lewy Body Disease (genetics)</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Mutation (genetics)</term>
<term>Risk Factors</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en">
<term>Glucosylceramidase</term>
</keywords>
<keywords scheme="MESH" qualifier="diagnosis" xml:lang="en">
<term>Lewy Body Disease</term>
</keywords>
<keywords scheme="MESH" qualifier="epidemiology" xml:lang="en">
<term>Lewy Body Disease</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en">
<term>Lewy Body Disease</term>
<term>Mutation</term>
</keywords>
<keywords scheme="MESH" qualifier="methods" xml:lang="en">
<term>Genetic Association Studies</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Aged</term>
<term>Aged, 80 and over</term>
<term>Case-Control Studies</term>
<term>Female</term>
<term>Genotype</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Risk Factors</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<sec id="S1">
<title>Importance</title>
<p id="P1">While mutations in glucocerebrosidase (
<italic>GBA1</italic>
) are associated with an increased risk for Parkinson disease (PD), it is important to establish whether such mutations are also a common risk factor for other Lewy body disorders.</p>
</sec>
<sec id="S2">
<title>Objective</title>
<p id="P2">To establish whether
<italic>GBA1</italic>
mutations are a risk factor for dementia with Lewy bodies (DLB).</p>
</sec>
<sec id="S3">
<title>Design</title>
<p id="P3">We compared genotype data on patients and controls from 11 centers. Data concerning demographics, age at onset, disease duration, and clinical and pathological features were collected when available. We conducted pooled analyses using logistic regression to investigate
<italic>GBA1</italic>
mutation carrier status as predicting DLB or PD with dementia status, using common control subjects as a reference group. Random-effects meta-analyses were conducted to account for additional heterogeneity.</p>
</sec>
<sec id="S4">
<title>Setting</title>
<p id="P4">Eleven centers from sites around the world performing genotyping.</p>
</sec>
<sec id="S5">
<title>Participants</title>
<p id="P5">Seven hundred twenty-one cases met diagnostic criteria for DLB and 151 had PD with dementia. We compared these cases with 1962 controls from the same centers matched for age, sex, and ethnicity.</p>
</sec>
<sec id="S6">
<title>Main Outcome Measures</title>
<p id="P6">Frequency of
<italic>GBA1</italic>
mutations in cases and controls.</p>
</sec>
<sec id="S7">
<title>Results</title>
<p id="P7">We found a significant association between
<italic>GBA1</italic>
mutation carrier status and DLB, with an odds ratio of 8.28 (95% CI, 4.78–14.88). The odds ratio for PD with dementia was 6.48 (95% CI, 2.53–15.37). The mean age at diagnosis of DLB was earlier in
<italic>GBA1</italic>
mutation carriers than in noncarriers (63.5 vs 68.9 years;
<italic>P<</italic>
.001), with higher disease severity scores.</p>
</sec>
<sec id="S8">
<title>Conclusions and Relevance</title>
<p id="P8">Mutations in
<italic>GBA1</italic>
are a significant risk factor for DLB.
<italic>GBA1</italic>
mutations likely play an even larger role in the genetic etiology of DLB than in PD, providing insight into the role of glucocerebrosidase in Lewy body disease.</p>
</sec>
</div>
</front>
</TEI>
<affiliations>
<list></list>
<tree>
<noCountry>
<name sortKey="Annesi, Grazia" sort="Annesi, Grazia" uniqKey="Annesi G" first="Grazia" last="Annesi">Grazia Annesi</name>
<name sortKey="Berg, Daniela" sort="Berg, Daniela" uniqKey="Berg D" first="Daniela" last="Berg">Daniela Berg</name>
<name sortKey="Bilbao, Juan M" sort="Bilbao, Juan M" uniqKey="Bilbao J" first="Juan M." last="Bilbao">Juan M. Bilbao</name>
<name sortKey="Black, Sandra E" sort="Black, Sandra E" uniqKey="Black S" first="Sandra E." last="Black">Sandra E. Black</name>
<name sortKey="Bras, Jose" sort="Bras, Jose" uniqKey="Bras J" first="Jose" last="Bras">Jose Bras</name>
<name sortKey="Brice, Alexis" sort="Brice, Alexis" uniqKey="Brice A" first="Alexis" last="Brice">Alexis Brice</name>
<name sortKey="Brockmann, Kathrin" sort="Brockmann, Kathrin" uniqKey="Brockmann K" first="Kathrin" last="Brockmann">Kathrin Brockmann</name>
<name sortKey="Chinnery, Patrick F" sort="Chinnery, Patrick F" uniqKey="Chinnery P" first="Patrick F." last="Chinnery">Patrick F. Chinnery</name>
<name sortKey="Clark, Lorraine" sort="Clark, Lorraine" uniqKey="Clark L" first="Lorraine" last="Clark">Lorraine Clark</name>
<name sortKey="Cras, Patrick" sort="Cras, Patrick" uniqKey="Cras P" first="Patrick" last="Cras">Patrick Cras</name>
<name sortKey="Crosiers, David" sort="Crosiers, David" uniqKey="Crosiers D" first="David" last="Crosiers">David Crosiers</name>
<name sortKey="Davidson, Yvonne" sort="Davidson, Yvonne" uniqKey="Davidson Y" first="Yvonne" last="Davidson">Yvonne Davidson</name>
<name sortKey="De Deyn, Peter Paul" sort="De Deyn, Peter Paul" uniqKey="De Deyn P" first="Peter Paul" last="De Deyn">Peter Paul De Deyn</name>
<name sortKey="De Marco, Elvira Valeria" sort="De Marco, Elvira Valeria" uniqKey="De Marco E" first="Elvira Valeria" last="De Marco">Elvira Valeria De Marco</name>
<name sortKey="Duran, Raquel" sort="Duran, Raquel" uniqKey="Duran R" first="Raquel" last="Duran">Raquel Duran</name>
<name sortKey="Durr, Alexandra" sort="Durr, Alexandra" uniqKey="Durr A" first="Alexandra" last="Durr">Alexandra Durr</name>
<name sortKey="Duyckaerts, Charles" sort="Duyckaerts, Charles" uniqKey="Duyckaerts C" first="Charles" last="Duyckaerts">Charles Duyckaerts</name>
<name sortKey="Engelborghs, Sebastiaan" sort="Engelborghs, Sebastiaan" uniqKey="Engelborghs S" first="Sebastiaan" last="Engelborghs">Sebastiaan Engelborghs</name>
<name sortKey="Foroud, Tatiana" sort="Foroud, Tatiana" uniqKey="Foroud T" first="Tatiana" last="Foroud">Tatiana Foroud</name>
<name sortKey="Gasser, Thomas" sort="Gasser, Thomas" uniqKey="Gasser T" first="Thomas" last="Gasser">Thomas Gasser</name>
<name sortKey="Ghetti, Bernardino" sort="Ghetti, Bernardino" uniqKey="Ghetti B" first="Bernardino" last="Ghetti">Bernardino Ghetti</name>
<name sortKey="Giasson, Benoit I" sort="Giasson, Benoit I" uniqKey="Giasson B" first="Benoit I." last="Giasson">Benoit I. Giasson</name>
<name sortKey="Gibbons, Linda" sort="Gibbons, Linda" uniqKey="Gibbons L" first="Linda" last="Gibbons">Linda Gibbons</name>
<name sortKey="Halliday, Glenda" sort="Halliday, Glenda" uniqKey="Halliday G" first="Glenda" last="Halliday">Glenda Halliday</name>
<name sortKey="Halliwell, Nicola" sort="Halliwell, Nicola" uniqKey="Halliwell N" first="Nicola" last="Halliwell">Nicola Halliwell</name>
<name sortKey="Hardy, John" sort="Hardy, John" uniqKey="Hardy J" first="John" last="Hardy">John Hardy</name>
<name sortKey="Harris, Jenny" sort="Harris, Jenny" uniqKey="Harris J" first="Jenny" last="Harris">Jenny Harris</name>
<name sortKey="Honig, Lawrence S" sort="Honig, Lawrence S" uniqKey="Honig L" first="Lawrence S." last="Honig">Lawrence S. Honig</name>
<name sortKey="Hurtig, Howard I" sort="Hurtig, Howard I" uniqKey="Hurtig H" first="Howard I." last="Hurtig">Howard I. Hurtig</name>
<name sortKey="Keller, Margaux" sort="Keller, Margaux" uniqKey="Keller M" first="Margaux" last="Keller">Margaux Keller</name>
<name sortKey="Klebe, Stephan" sort="Klebe, Stephan" uniqKey="Klebe S" first="Stephan" last="Klebe">Stephan Klebe</name>
<name sortKey="Knight, Melanie A" sort="Knight, Melanie A" uniqKey="Knight M" first="Melanie A." last="Knight">Melanie A. Knight</name>
<name sortKey="Kurzawa Akanbi, Marzena" sort="Kurzawa Akanbi, Marzena" uniqKey="Kurzawa Akanbi M" first="Marzena" last="Kurzawa-Akanbi">Marzena Kurzawa-Akanbi</name>
<name sortKey="Landazabal, Claudia" sort="Landazabal, Claudia" uniqKey="Landazabal C" first="Claudia" last="Landazabal">Claudia Landazabal</name>
<name sortKey="Lesage, Suzanne" sort="Lesage, Suzanne" uniqKey="Lesage S" first="Suzanne" last="Lesage">Suzanne Lesage</name>
<name sortKey="Lopez, Grisel" sort="Lopez, Grisel" uniqKey="Lopez G" first="Grisel" last="Lopez">Grisel Lopez</name>
<name sortKey="Maetzler, Walter" sort="Maetzler, Walter" uniqKey="Maetzler W" first="Walter" last="Maetzler">Walter Maetzler</name>
<name sortKey="Mann, David M A" sort="Mann, David M A" uniqKey="Mann D" first="David M. A." last="Mann">David M. A. Mann</name>
<name sortKey="Marder, Karen" sort="Marder, Karen" uniqKey="Marder K" first="Karen" last="Marder">Karen Marder</name>
<name sortKey="Masellis, Mario" sort="Masellis, Mario" uniqKey="Masellis M" first="Mario" last="Masellis">Mario Masellis</name>
<name sortKey="Mckeith, Ian G" sort="Mckeith, Ian G" uniqKey="Mckeith I" first="Ian G." last="Mckeith">Ian G. Mckeith</name>
<name sortKey="Morris, Christopher M" sort="Morris, Christopher M" uniqKey="Morris C" first="Christopher M." last="Morris">Christopher M. Morris</name>
<name sortKey="Nalls, Michael A" sort="Nalls, Michael A" uniqKey="Nalls M" first="Michael A." last="Nalls">Michael A. Nalls</name>
<name sortKey="Nichols, William C" sort="Nichols, William C" uniqKey="Nichols W" first="William C." last="Nichols">William C. Nichols</name>
<name sortKey="Novellino, Fabiana" sort="Novellino, Fabiana" uniqKey="Novellino F" first="Fabiana" last="Novellino">Fabiana Novellino</name>
<name sortKey="Pankratz, Nathan" sort="Pankratz, Nathan" uniqKey="Pankratz N" first="Nathan" last="Pankratz">Nathan Pankratz</name>
<name sortKey="Pickering Brown, Stuart" sort="Pickering Brown, Stuart" uniqKey="Pickering Brown S" first="Stuart" last="Pickering-Brown">Stuart Pickering-Brown</name>
<name sortKey="Quattrone, Aldo" sort="Quattrone, Aldo" uniqKey="Quattrone A" first="Aldo" last="Quattrone">Aldo Quattrone</name>
<name sortKey="Rogaeva, Ekaterina" sort="Rogaeva, Ekaterina" uniqKey="Rogaeva E" first="Ekaterina" last="Rogaeva">Ekaterina Rogaeva</name>
<name sortKey="Sheerin, Una Marie" sort="Sheerin, Una Marie" uniqKey="Sheerin U" first="Una-Marie" last="Sheerin">Una-Marie Sheerin</name>
<name sortKey="Sidransky, Ellen" sort="Sidransky, Ellen" uniqKey="Sidransky E" first="Ellen" last="Sidransky">Ellen Sidransky</name>
<name sortKey="Singleton, Andrew B" sort="Singleton, Andrew B" uniqKey="Singleton A" first="Andrew B." last="Singleton">Andrew B. Singleton</name>
<name sortKey="Snowden, Julie" sort="Snowden, Julie" uniqKey="Snowden J" first="Julie" last="Snowden">Julie Snowden</name>
<name sortKey="Tayebi, Nahid" sort="Tayebi, Nahid" uniqKey="Tayebi N" first="Nahid" last="Tayebi">Nahid Tayebi</name>
<name sortKey="Theuns, Jessie" sort="Theuns, Jessie" uniqKey="Theuns J" first="Jessie" last="Theuns">Jessie Theuns</name>
<name sortKey="Trojanowski, John Q" sort="Trojanowski, John Q" uniqKey="Trojanowski J" first="John Q." last="Trojanowski">John Q. Trojanowski</name>
<name sortKey="Van Broeckhoven, Christine" sort="Van Broeckhoven, Christine" uniqKey="Van Broeckhoven C" first="Christine" last="Van Broeckhoven">Christine Van Broeckhoven</name>
<name sortKey="Wolfsberg, Tyra G" sort="Wolfsberg, Tyra G" uniqKey="Wolfsberg T" first="Tyra G." last="Wolfsberg">Tyra G. Wolfsberg</name>
</noCountry>
</tree>
</affiliations>
</record>

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