AustralieFrV1, Main, Exploration, bibRecord, 008503

A large-scale international meta-analysis of paraoxonase gene polymorphisms in sporadic ALS

Identifieur interne : 008503 ( Main/Exploration ); précédent : 008502; suivant : 008504

A large-scale international meta-analysis of paraoxonase gene polymorphisms in sporadic ALS

Auteurs : A.-M. Wills [États-Unis] ; S. Cronin [Irlande (pays)] ; A. Slowik [Pologne] ; D. Kasperaviciute [Royaume-Uni] ; M. A. Van Es [Pays-Bas] ; J. M. Morahan [Australie] ; P. N. Valdmanis [Canada] ; V. Meininger [France] ; J. Melki [Israël] ; C. E. Shaw [Royaume-Uni] ; G. A. Rouleau [Canada] ; E. M. C. Fisher [Royaume-Uni] ; P. J. Shaw [Royaume-Uni] ; K. E. Morrison [Royaume-Uni] ; R. Pamphlett [Australie] ; L. H. Van Den Berg [Pays-Bas] ; D. A. Figlewicz [États-Unis, Canada] ; P. M. Andersen [Suède] ; A. Al-Chalabi [Royaume-Uni] ; O. Hardiman [Irlande (pays)] ; S. Purcell [États-Unis] ; J. E. Landers [États-Unis] ; Rh. Jr Brown [États-Unis]

Source :

Neurology [ 0028-3878 ] ; 2009.

RBID : Pascal:09-0316558

Descripteurs français

Pascal (Inist)
- Pathologie du système nerveux, Aryldialkylphosphatase, Polymorphisme, Sporadique.

English descriptors

KwdEn :
- Aryldialkylphosphatase, Nervous system diseases, Polymorphism, Sporadic.

Abstract

Background: Six candidate gene studies report a genetic association of DNA variants within the paraoxonase locus with sporadic amyotrophic lateral sclerosis (ALS). However, several other large studies, including five genome-wide association studies, have not duplicated this finding. Methods: We conducted a meta-analysis of 10 published studies and one unpublished study of the paraoxonase locus, encompassing 4,037 ALS cases and 4,609 controls, including genome-wide association data from 2,018 ALS cases and 2,425 controls. Results: The combined fixed effects odds ratio (OR) for rs662 (PON1 Q192R) was 1.09 (95% confidence interval [CI],1.02-1.16, p = 0.01); the genotypic OR for RR homozygotes at Q192R was 1.25 (95% CI, 1.07-1.45, p ₌ 0.0004); the combined OR for rs854560 (PON1 L55M) was 0.97 (95% CI, 0.86-1.10, p ₌ 0.62); the OR for rs10487132 (PON2) was 1.08 (95% CI, 0.92-1.27, p ₌ 0.35). Although the rs662 polymorphism reached a nominal level of significance, no polymorphism was significant after multiple testing correction. In the subanalysis of samples with genome-wide data from which population outliers were removed, rs662 had an OR of 1.06 (95% CI, 0.97-1.16, p ₌ 0.22). Conclusions: In contrast to previous positive smaller studies, our genetic meta-analysis showed no significant association of amyotrophic lateral sclerosis (ALS) with the PON locus. This is the largest meta-analysis of a candidate gene in ALS to date and the first ALS meta-analysis to include data from whole genome association studies. The findings reinforce the need for much larger and more collaborative investigations of the genetic determinants of ALS.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2707108

Affiliations:

Le document en format XML

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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">A large-scale international meta-analysis of paraoxonase gene polymorphisms in sporadic ALS</title>
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<author><name sortKey="Morrison, K E" sort="Morrison, K E" uniqKey="Morrison K" first="K. E." last="Morrison">K. E. Morrison</name>
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<author><name sortKey="Pamphlett, R" sort="Pamphlett, R" uniqKey="Pamphlett R" first="R." last="Pamphlett">R. Pamphlett</name>
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<placeName><settlement type="city">Sydney</settlement>
<region type="état">Nouvelle-Galles du Sud</region>
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<orgName type="university">Université de Sydney</orgName>
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<author><name sortKey="Van Den Berg, L H" sort="Van Den Berg, L H" uniqKey="Van Den Berg L" first="L. H." last="Van Den Berg">L. H. Van Den Berg</name>
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<author><name sortKey="Figlewicz, D A" sort="Figlewicz, D A" uniqKey="Figlewicz D" first="D. A." last="Figlewicz">D. A. Figlewicz</name>
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<s3>USA</s3>
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<country>États-Unis</country>
<wicri:noRegion>University of Michigan</wicri:noRegion>
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<author><name sortKey="Andersen, P M" sort="Andersen, P M" uniqKey="Andersen P" first="P. M." last="Andersen">P. M. Andersen</name>
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<author><name sortKey="Al Chalabi, A" sort="Al Chalabi, A" uniqKey="Al Chalabi A" first="A." last="Al-Chalabi">A. Al-Chalabi</name>
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<s2>Charlestown</s2>
<s3>USA</s3>
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<wicri:noRegion>Cecil B. Day Neuromuscular Research Laboratory Massachusetts General Hospital</wicri:noRegion>
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<author><name sortKey="Brown, Rh Jr" sort="Brown, Rh Jr" uniqKey="Brown R" first="Rh. Jr" last="Brown">Rh. Jr Brown</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Cecil B. Day Neuromuscular Research Laboratory Massachusetts General Hospital</s1>
<s2>Charlestown</s2>
<s3>USA</s3>
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<series><title level="j" type="main">Neurology</title>
<title level="j" type="abbreviated">Neurology</title>
<idno type="ISSN">0028-3878</idno>
<imprint><date when="2009">2009</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><title level="j" type="main">Neurology</title>
<title level="j" type="abbreviated">Neurology</title>
<idno type="ISSN">0028-3878</idno>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aryldialkylphosphatase</term>
<term>Nervous system diseases</term>
<term>Polymorphism</term>
<term>Sporadic</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Pathologie du   système nerveux</term>
<term>Aryldialkylphosphatase</term>
<term>Polymorphisme</term>
<term>Sporadique</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Background: Six candidate gene studies report a genetic association of DNA variants within the paraoxonase locus with sporadic amyotrophic lateral sclerosis (ALS). However, several other large studies, including five genome-wide association studies, have not duplicated this finding. Methods: We conducted a meta-analysis of 10 published studies and one unpublished study of the paraoxonase locus, encompassing 4,037 ALS cases and 4,609 controls, including genome-wide association data from 2,018 ALS cases and 2,425 controls. Results: The combined fixed effects odds ratio (OR) for rs662 (PON1 Q192R) was 1.09 (95% confidence interval [CI],1.02-1.16, p = 0.01); the genotypic OR for RR homozygotes at Q192R was 1.25 (95% CI, 1.07-1.45, p <sub>=</sub>
 0.0004); the combined OR for rs854560 (PON1 L55M) was 0.97 (95% CI, 0.86-1.10, p <sub>=</sub>
 0.62); the OR for rs10487132 (PON2) was 1.08 (95% CI, 0.92-1.27, p <sub>=</sub>
 0.35). Although the rs662 polymorphism reached a nominal level of significance, no polymorphism was significant after multiple testing correction. In the subanalysis of samples with genome-wide data from which population outliers were removed, rs662 had an OR of 1.06 (95% CI, 0.97-1.16, p <sub>=</sub>
 0.22). Conclusions: In contrast to previous positive smaller studies, our genetic meta-analysis showed no significant association of amyotrophic lateral sclerosis (ALS) with the PON locus. This is the largest meta-analysis of a candidate gene in ALS to date and the first ALS meta-analysis to include data from whole genome association studies. The findings reinforce the need for much larger and more collaborative investigations of the genetic determinants of ALS.</div>
</front>
</TEI>
<affiliations><list><country><li>Australie</li>
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<li>États-Unis</li>
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<li>Midlands de l'Ouest</li>
<li>Nouvelle-Galles du Sud</li>
<li>Utrecht (province)</li>
<li>Île-de-France</li>
</region>
<settlement><li>Birmingham</li>
<li>Londres</li>
<li>Paris</li>
<li>Sydney</li>
<li>Utrecht</li>
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<orgName><li>Université de Birmingham</li>
<li>Université de Sydney</li>
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<tree><country name="États-Unis"><noRegion><name sortKey="Wills, A M" sort="Wills, A M" uniqKey="Wills A" first="A.-M." last="Wills">A.-M. Wills</name>
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</region>
<name sortKey="Al Chalabi, A" sort="Al Chalabi, A" uniqKey="Al Chalabi A" first="A." last="Al-Chalabi">A. Al-Chalabi</name>
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<name sortKey="Morrison, K E" sort="Morrison, K E" uniqKey="Morrison K" first="K. E." last="Morrison">K. E. Morrison</name>
<name sortKey="Shaw, C E" sort="Shaw, C E" uniqKey="Shaw C" first="C. E." last="Shaw">C. E. Shaw</name>
<name sortKey="Shaw, P J" sort="Shaw, P J" uniqKey="Shaw P" first="P. J." last="Shaw">P. J. Shaw</name>
</country>
<country name="Pays-Bas"><region name="Utrecht (province)"><name sortKey="Van Es, M A" sort="Van Es, M A" uniqKey="Van Es M" first="M. A." last="Van Es">M. A. Van Es</name>
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<name sortKey="Van Den Berg, L H" sort="Van Den Berg, L H" uniqKey="Van Den Berg L" first="L. H." last="Van Den Berg">L. H. Van Den Berg</name>
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<country name="Australie"><region name="Nouvelle-Galles du Sud"><name sortKey="Morahan, J M" sort="Morahan, J M" uniqKey="Morahan J" first="J. M." last="Morahan">J. M. Morahan</name>
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<name sortKey="Morahan, J M" sort="Morahan, J M" uniqKey="Morahan J" first="J. M." last="Morahan">J. M. Morahan</name>
<name sortKey="Pamphlett, R" sort="Pamphlett, R" uniqKey="Pamphlett R" first="R." last="Pamphlett">R. Pamphlett</name>
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<country name="France"><region name="Île-de-France"><name sortKey="Meininger, V" sort="Meininger, V" uniqKey="Meininger V" first="V." last="Meininger">V. Meininger</name>
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A large-scale international meta-analysis of paraoxonase gene polymorphisms in sporadic ALS

A large-scale international meta-analysis of paraoxonase gene polymorphisms in sporadic ALS

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