Mitochondrial Polymorphisms Significantly Reduce the Risk of Parkinson Disease
Identifieur interne : 000055 ( Ncbi/Curation ); précédent : 000054; suivant : 000056Mitochondrial Polymorphisms Significantly Reduce the Risk of Parkinson Disease
Auteurs : Joelle Van ; Kristin Nicodemus ; Eden Martin ; William Scott ; Martha Nance [États-Unis] ; Ray Watts ; Jean Hubble [États-Unis] ; Jonathan Haines [États-Unis] ; William Koller ; Kelly Lyons ; Rajesh Pahwa [États-Unis] ; Matthew Stern ; Amy Colcher ; Bradley Hiner [États-Unis] ; Joseph Jankovic [États-Unis] ; William Ondo ; Fred Allen [États-Unis] ; Christopher Goetz ; Gary Small ; Frank Mastaglia [Australie] ; Jeffrey Stajich ; Adam Mclaurin ; Lefkos Middleton [Royaume-Uni] ; Burton Scott [États-Unis] ; Donald Schmechel ; Margaret Pericak ; Jeffery VanceSource :
- American Journal of Human Genetics [ 0002-9297 ] ; 2003.
English descriptors
- KwdEn :
- DNA, Mitochondrial (genetics), Europe (ethnology), European Continental Ancestry Group (genetics), Genotype, Great Britain, Haplotypes, Humans, Mitochondria (genetics), Mitochondria (pathology), Molecular Sequence Data, Parkinson Disease (epidemiology), Parkinson Disease (genetics), Polymorphism, Genetic, Polymorphism, Single Nucleotide, Reference Values, Risk Factors, United States.
- MESH :
- chemical , genetics : DNA, Mitochondrial.
- geographic , ethnology : Europe.
- epidemiology : Parkinson Disease.
- genetics : European Continental Ancestry Group, Mitochondria, Parkinson Disease.
- pathology : Mitochondria.
- Genotype, Great Britain, Haplotypes, Humans, Molecular Sequence Data, Polymorphism, Genetic, Polymorphism, Single Nucleotide, Reference Values, Risk Factors, United States.
Abstract
Mitochondrial (mt) impairment, particularly within complex I of the electron transport system, has been implicated in the pathogenesis of Parkinson disease (PD). More than half of mitochondrially encoded polypeptides form part of the reduced nicotinamide adenine dinucleotide dehydrogenase (NADH) complex I enzyme. To test the hypothesis that mtDNA variation contributes to PD expression, we genotyped 10 single-nucleotide polymorphisms (SNPs) that define the European mtDNA haplogroups in 609 white patients with PD and 340 unaffected white control subjects. Overall, individuals classified as haplogroup J (odds ratio [OR] 0.55; 95% confidence interval [CI] 0.34–0.91;
Url:
PubMed: 12618962
PubMed Central: 1180345
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Ray Watts<affiliation><nlm:aff id="N0x8a5c020.0x8bc2b50">Department of Neurology, Emory University School of Medicine, Atlanta;</nlm:aff>
<wicri:noCountry code="subfield">Atlanta</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="N0x8a5c020.0x8bc2b50">Department of Neurology, University of Miami School of Medicine, Miami;</nlm:aff>
<wicri:noCountry code="subfield">Miami</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="N0x8a5c020.0x8bc2b50">Department of Neurology, University of Miami School of Medicine, Miami;</nlm:aff>
<wicri:noCountry code="subfield">Miami</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="N0x8a5c020.0x8bc2b50">Department of Neurology, University of Pennsylvania Health System, Philadelphia;</nlm:aff>
<wicri:noCountry code="subfield">Philadelphia</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="N0x8a5c020.0x8bc2b50">Department of Neurology, University of Pennsylvania Health System, Philadelphia;</nlm:aff>
<wicri:noCountry code="subfield">Philadelphia</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="N0x8a5c020.0x8bc2b50">Department of Neurology, Baylor College of Medicine, Houston;</nlm:aff>
<wicri:noCountry code="subfield">Houston</wicri:noCountry>
<country>États-Unis</country>
<placeName><settlement type="city">Houston</settlement>
<region type="state">Texas</region>
</placeName>
<orgName type="university" n="3">Baylor College of Medicine</orgName>
</affiliation>
<affiliation><nlm:aff id="N0x8a5c020.0x8bc2b50">Department of Neurology, Baylor College of Medicine, Houston;</nlm:aff>
<wicri:noCountry code="subfield">Houston</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="N0x8a5c020.0x8bc2b50">Department of Neurological Sciences, Rush-Presbyterian–St. Luke’s Hospital, Chicago; Departments of</nlm:aff>
<wicri:noCountry code="subfield">Chicago; Departments of</wicri:noCountry>
</affiliation>
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<author><name sortKey="Lyons, Kelly" sort="Lyons, Kelly" uniqKey="Lyons K" first="Kelly" last="Lyons">Kelly Lyons</name>
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<author><name sortKey="Jankovic, Joseph" sort="Jankovic, Joseph" uniqKey="Jankovic J" first="Joseph" last="Jankovic">Joseph Jankovic</name>
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<wicri:noCountry code="subfield">Chicago; Departments of</wicri:noCountry>
</affiliation>
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<affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="N0x8a5c020.0x8bc2b50">Centre for Neuromuscular and Neurological Disorders, University of Western Australia, Perth, Australia</nlm:aff>
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<author><name sortKey="Scott, Burton L" sort="Scott, Burton L" uniqKey="Scott B" first="Burton" last="Scott">Burton Scott</name>
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</placeName>
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</affiliation>
</author>
<author><name sortKey="Schmechel, Donald E" sort="Schmechel, Donald E" uniqKey="Schmechel D" first="Donald" last="Schmechel">Donald Schmechel</name>
<affiliation><nlm:aff wicri:cut=", and" id="N0x8a5c020.0x8bc2b50">Department of Medicine</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Pericak Vance, Margaret A" sort="Pericak Vance, Margaret A" uniqKey="Pericak Vance M" first="Margaret" last="Pericak">Margaret Pericak</name>
<affiliation><nlm:aff>NONE</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Vance, Jeffery M" sort="Vance, Jeffery M" uniqKey="Vance J" first="Jeffery" last="Vance">Jeffery Vance</name>
<affiliation><nlm:aff>NONE</nlm:aff>
</affiliation>
</author>
</titleStmt>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Mitochondrial Polymorphisms Significantly Reduce the Risk of Parkinson Disease</title>
<author><name sortKey="Van Der Walt, Joelle M" sort="Van Der Walt, Joelle M" uniqKey="Van Der Walt J" first="Joelle" last="Van">Joelle Van</name>
<affiliation><nlm:aff>NONE</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Nicodemus, Kristin K" sort="Nicodemus, Kristin K" uniqKey="Nicodemus K" first="Kristin" last="Nicodemus">Kristin Nicodemus</name>
<affiliation><nlm:aff>NONE</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Martin, Eden R" sort="Martin, Eden R" uniqKey="Martin E" first="Eden" last="Martin">Eden Martin</name>
<affiliation><nlm:aff>NONE</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Scott, William K" sort="Scott, William K" uniqKey="Scott W" first="William" last="Scott">William Scott</name>
<affiliation><nlm:aff>NONE</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Nance, Martha A" sort="Nance, Martha A" uniqKey="Nance M" first="Martha" last="Nance">Martha Nance</name>
<affiliation wicri:level="2"><nlm:aff id="N0x8a5c020.0x8bc2b50">Struthers Parkinson Center, Golden Valley, MN;</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Minnesota</region>
</placeName>
<wicri:cityArea>Struthers Parkinson Center, Golden Valley</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Watts, Ray L" sort="Watts, Ray L" uniqKey="Watts R" first="Ray" last="Watts">Ray Watts</name>
<affiliation><nlm:aff id="N0x8a5c020.0x8bc2b50">Department of Neurology, Emory University School of Medicine, Atlanta;</nlm:aff>
<wicri:noCountry code="subfield">Atlanta</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Hubble, Jean P" sort="Hubble, Jean P" uniqKey="Hubble J" first="Jean" last="Hubble">Jean Hubble</name>
<affiliation wicri:level="2"><nlm:aff id="N0x8a5c020.0x8bc2b50">Department of Neurology, Ohio State University, Columbus, OH;</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Ohio</region>
</placeName>
<wicri:cityArea>Department of Neurology, Ohio State University, Columbus</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Haines, Jonathan L" sort="Haines, Jonathan L" uniqKey="Haines J" first="Jonathan" last="Haines">Jonathan Haines</name>
<affiliation wicri:level="2"><nlm:aff id="N0x8a5c020.0x8bc2b50">Program in Human Genetics, Vanderbilt University Medical Center, Nashville, TN;</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Tennessee</region>
</placeName>
<wicri:cityArea>Program in Human Genetics, Vanderbilt University Medical Center, Nashville</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Koller, William C" sort="Koller, William C" uniqKey="Koller W" first="William" last="Koller">William Koller</name>
<affiliation><nlm:aff id="N0x8a5c020.0x8bc2b50">Department of Neurology, University of Miami School of Medicine, Miami;</nlm:aff>
<wicri:noCountry code="subfield">Miami</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Lyons, Kelly" sort="Lyons, Kelly" uniqKey="Lyons K" first="Kelly" last="Lyons">Kelly Lyons</name>
<affiliation><nlm:aff id="N0x8a5c020.0x8bc2b50">Department of Neurology, University of Miami School of Medicine, Miami;</nlm:aff>
<wicri:noCountry code="subfield">Miami</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Pahwa, Rajesh" sort="Pahwa, Rajesh" uniqKey="Pahwa R" first="Rajesh" last="Pahwa">Rajesh Pahwa</name>
<affiliation wicri:level="2"><nlm:aff id="N0x8a5c020.0x8bc2b50">Department of Neurology, University of Kansas Medical Center, Kansas City, KS;</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Kansas</region>
</placeName>
<wicri:cityArea>Department of Neurology, University of Kansas Medical Center, Kansas City</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Stern, Matthew B" sort="Stern, Matthew B" uniqKey="Stern M" first="Matthew" last="Stern">Matthew Stern</name>
<affiliation><nlm:aff id="N0x8a5c020.0x8bc2b50">Department of Neurology, University of Pennsylvania Health System, Philadelphia;</nlm:aff>
<wicri:noCountry code="subfield">Philadelphia</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Colcher, Amy" sort="Colcher, Amy" uniqKey="Colcher A" first="Amy" last="Colcher">Amy Colcher</name>
<affiliation><nlm:aff id="N0x8a5c020.0x8bc2b50">Department of Neurology, University of Pennsylvania Health System, Philadelphia;</nlm:aff>
<wicri:noCountry code="subfield">Philadelphia</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Hiner, Bradley C" sort="Hiner, Bradley C" uniqKey="Hiner B" first="Bradley" last="Hiner">Bradley Hiner</name>
<affiliation wicri:level="2"><nlm:aff id="N0x8a5c020.0x8bc2b50">Department of Neurology, Marshfield Clinic, Marshfield, WI;</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Wisconsin</region>
</placeName>
<wicri:cityArea>Department of Neurology, Marshfield Clinic, Marshfield</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Jankovic, Joseph" sort="Jankovic, Joseph" uniqKey="Jankovic J" first="Joseph" last="Jankovic">Joseph Jankovic</name>
<affiliation><nlm:aff id="N0x8a5c020.0x8bc2b50">Department of Neurology, Baylor College of Medicine, Houston;</nlm:aff>
<wicri:noCountry code="subfield">Houston</wicri:noCountry>
<country>États-Unis</country>
<placeName><settlement type="city">Houston</settlement>
<region type="state">Texas</region>
</placeName>
<orgName type="university" n="3">Baylor College of Medicine</orgName>
</affiliation>
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<author><name sortKey="Ondo, William G" sort="Ondo, William G" uniqKey="Ondo W" first="William" last="Ondo">William Ondo</name>
<affiliation><nlm:aff id="N0x8a5c020.0x8bc2b50">Department of Neurology, Baylor College of Medicine, Houston;</nlm:aff>
<wicri:noCountry code="subfield">Houston</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Allen Jr, Fred H" sort="Allen Jr, Fred H" uniqKey="Allen Jr F" first="Fred" last="Allen">Fred Allen</name>
<affiliation wicri:level="2"><nlm:aff id="N0x8a5c020.0x8bc2b50">Carolina Neurologic Clinic, Charlotte, NC;</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Caroline du Nord</region>
</placeName>
<wicri:cityArea>Carolina Neurologic Clinic, Charlotte</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Goetz, Christopher G" sort="Goetz, Christopher G" uniqKey="Goetz C" first="Christopher" last="Goetz">Christopher Goetz</name>
<affiliation><nlm:aff id="N0x8a5c020.0x8bc2b50">Department of Neurological Sciences, Rush-Presbyterian–St. Luke’s Hospital, Chicago; Departments of</nlm:aff>
<wicri:noCountry code="subfield">Chicago; Departments of</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Small, Gary W" sort="Small, Gary W" uniqKey="Small G" first="Gary" last="Small">Gary Small</name>
<affiliation><nlm:aff>NONE</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Mastaglia, Frank" sort="Mastaglia, Frank" uniqKey="Mastaglia F" first="Frank" last="Mastaglia">Frank Mastaglia</name>
<affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="N0x8a5c020.0x8bc2b50">Centre for Neuromuscular and Neurological Disorders, University of Western Australia, Perth, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Centre for Neuromuscular and Neurological Disorders, University of Western Australia, Perth</wicri:regionArea>
<wicri:noRegion>Perth</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Stajich, Jeffrey M" sort="Stajich, Jeffrey M" uniqKey="Stajich J" first="Jeffrey" last="Stajich">Jeffrey Stajich</name>
<affiliation><nlm:aff>NONE</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Mclaurin, Adam C" sort="Mclaurin, Adam C" uniqKey="Mclaurin A" first="Adam" last="Mclaurin">Adam Mclaurin</name>
<affiliation><nlm:aff>NONE</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Middleton, Lefkos T" sort="Middleton, Lefkos T" uniqKey="Middleton L" first="Lefkos" last="Middleton">Lefkos Middleton</name>
<affiliation wicri:level="1"><nlm:aff id="N0x8a5c020.0x8bc2b50">GlaxoSmithKline Research and Development, Greenford, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>GlaxoSmithKline Research and Development, Greenford</wicri:regionArea>
<wicri:noRegion>Greenford</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Scott, Burton L" sort="Scott, Burton L" uniqKey="Scott B" first="Burton" last="Scott">Burton Scott</name>
<affiliation wicri:level="2"><nlm:aff id="N0x8a5c020.0x8bc2b50">Struthers Parkinson Center, Golden Valley, MN;</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Minnesota</region>
</placeName>
<wicri:cityArea>Struthers Parkinson Center, Golden Valley</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Schmechel, Donald E" sort="Schmechel, Donald E" uniqKey="Schmechel D" first="Donald" last="Schmechel">Donald Schmechel</name>
<affiliation><nlm:aff wicri:cut=", and" id="N0x8a5c020.0x8bc2b50">Department of Medicine</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Pericak Vance, Margaret A" sort="Pericak Vance, Margaret A" uniqKey="Pericak Vance M" first="Margaret" last="Pericak">Margaret Pericak</name>
<affiliation><nlm:aff>NONE</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Vance, Jeffery M" sort="Vance, Jeffery M" uniqKey="Vance J" first="Jeffery" last="Vance">Jeffery Vance</name>
<affiliation><nlm:aff>NONE</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">American Journal of Human Genetics</title>
<idno type="ISSN">0002-9297</idno>
<idno type="e-ISSN">1537-6605</idno>
<imprint><date when="2003">2003</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>DNA, Mitochondrial (genetics)</term>
<term>Europe (ethnology)</term>
<term>European Continental Ancestry Group (genetics)</term>
<term>Genotype</term>
<term>Great Britain</term>
<term>Haplotypes</term>
<term>Humans</term>
<term>Mitochondria (genetics)</term>
<term>Mitochondria (pathology)</term>
<term>Molecular Sequence Data</term>
<term>Parkinson Disease (epidemiology)</term>
<term>Parkinson Disease (genetics)</term>
<term>Polymorphism, Genetic</term>
<term>Polymorphism, Single Nucleotide</term>
<term>Reference Values</term>
<term>Risk Factors</term>
<term>United States</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>DNA, Mitochondrial</term>
</keywords>
<keywords scheme="MESH" type="geographic" qualifier="ethnology" xml:lang="en"><term>Europe</term>
</keywords>
<keywords scheme="MESH" qualifier="epidemiology" xml:lang="en"><term>Parkinson Disease</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>European Continental Ancestry Group</term>
<term>Mitochondria</term>
<term>Parkinson Disease</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Mitochondria</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Genotype</term>
<term>Great Britain</term>
<term>Haplotypes</term>
<term>Humans</term>
<term>Molecular Sequence Data</term>
<term>Polymorphism, Genetic</term>
<term>Polymorphism, Single Nucleotide</term>
<term>Reference Values</term>
<term>Risk Factors</term>
<term>United States</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>Mitochondrial (mt) impairment, particularly within complex I of the electron transport system, has been implicated in the pathogenesis of Parkinson disease (PD). More than half of mitochondrially encoded polypeptides form part of the reduced nicotinamide adenine dinucleotide dehydrogenase (NADH) complex I enzyme. To test the hypothesis that mtDNA variation contributes to PD expression, we genotyped 10 single-nucleotide polymorphisms (SNPs) that define the European mtDNA haplogroups in 609 white patients with PD and 340 unaffected white control subjects. Overall, individuals classified as haplogroup J (odds ratio [OR] 0.55; 95% confidence interval [CI] 0.34–0.91; <inline-formula><italic>P</italic>
=.02</inline-formula>
) or K (OR 0.52; 95% CI 0.30–0.90; <inline-formula><italic>P</italic>
=.02</inline-formula>
) demonstrated a significant decrease in risk of PD versus individuals carrying the most common haplogroup, H. Furthermore, a specific SNP that defines these two haplogroups, 10398G, is strongly associated with this protective effect (OR 0.53; 95% CI 0.39–0.73; <inline-formula><italic>P</italic>
=.0001</inline-formula>
). SNP 10398G causes a nonconservative amino acid change from threonine to alanine within the NADH dehydrogenase 3 (ND3) of complex I. After stratification by sex, this decrease in risk appeared stronger in women than in men (OR 0.43; 95% CI 0.27–0.71; <inline-formula><italic>P</italic>
=.0009</inline-formula>
). In addition, SNP 9055A of ATP6 demonstrated a protective effect for women (OR 0.45; 95% CI 0.22–0.93; <inline-formula><italic>P</italic>
=.03</inline-formula>
). Our results suggest that ND3 is an important factor in PD susceptibility among white individuals and could help explain the role of complex I in PD expression.</p>
</div>
</front>
</TEI>
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