Glutathione S-transferase omega-1 modifies age-at-onset of Alzheimer disease and Parkinson disease
Identifieur interne : 001421 ( Main/Curation ); précédent : 001420; suivant : 001422Glutathione S-transferase omega-1 modifies age-at-onset of Alzheimer disease and Parkinson disease
Auteurs : Yi Li ; Sofia Oliveira ; Puting Xu ; Eden Martin ; Judith Stenger ; Clemens Scherzer ; Michael Hauser ; William Scott ; Gary Small ; Martha Nance ; Ray Watts ; Jean Hubble ; William Koller ; Rajesh Pahwa ; Mathew Stern ; Bradley Hiner ; Joseph Jankovic [États-Unis] ; Christopher Goetz ; Frank Mastaglia ; Lefkos Middleton ; Allen Roses ; Ann Saunders ; Donald Schmechel ; Steven Gullans ; Jonathan Haines [États-Unis] ; John Gilbert ; Jeffery Vance ; Margaret PericakSource :
- Human Molecular Genetics [ 0964-6906 ] ; 2003-12-15.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Homme.
English descriptors
- KwdEn :
- Age of Onset, Aged, Alzheimer Disease (enzymology), Alzheimer Disease (genetics), Alzheimer disease, Chromosome Mapping, Chromosomes, Human, Pair 10, Female, Glutathione Transferase (genetics), Glutathione Transferase (metabolism), Glutathione transferase, Human, Humans, Linkage Disequilibrium, Lod Score, Male, Middle Aged, Molecular biology, Oligonucleotide Array Sequence Analysis, Onset time, Parkinson Disease (enzymology), Parkinson Disease (genetics), Parkinson disease, Polymorphism, Single Nucleotide.
- MESH :
- chemical , genetics : Glutathione Transferase.
- enzymology : Alzheimer Disease, Parkinson Disease.
- genetics : Alzheimer Disease, Parkinson Disease.
- chemical , metabolism : Glutathione Transferase.
- Age of Onset, Aged, Chromosome Mapping, Chromosomes, Human, Pair 10, Female, Humans, Linkage Disequilibrium, Lod Score, Male, Middle Aged, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide.
Abstract
We previously reported genetic linkage of loci controlling age-at-onset in Alzheimer disease (AD) and Parkinson's disease (PD) to a 15 cM region on chromosome 10q. Given the large number of genes in this initial starting region, we applied the process of ‘genomic convergence’ to prioritize and reduce the number of candidate genes for further analysis. As our second convergence factor we performed gene expression studies on hippocampus obtained from AD patients and controls. Analysis revealed that four of the genes [stearoyl-CoA desaturase; NADH-ubiquinone oxidoreductase 1 beta subcomplex 8; protease, serine 11; and glutathione S-transferase, omega-1 (GSTO1)] were significantly different in their expression between AD and controls and mapped to the 10q age-at-onset linkage region, the first convergence factor. Using 2814 samples from our AD dataset (1773 AD patients) and 1362 samples from our PD dataset (635 PD patients), allelic association studies for age-at-onset effects in AD and PD revealed no association for three of the candidates, but a significant association was found for GSTO1 (P=0.007) and a second transcribed member of the GST omega class, GSTO2 (P=0.005), located next to GSTO1. The functions of GSTO1 and GSTO2 are not well understood, but recent data suggest that GSTO1 maybe involved in the post-translational modification of the inflammatory cytokine interleukin-1β. This is provocative given reports of the possible role of inflammation in these two neurodegenerative disorders.
Url:
DOI: 10.1093/hmg/ddg357
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Age of Onset</term>
<term>Aged</term>
<term>Alzheimer Disease (enzymology)</term>
<term>Alzheimer Disease (genetics)</term>
<term>Alzheimer disease</term>
<term>Chromosome Mapping</term>
<term>Chromosomes, Human, Pair 10</term>
<term>Female</term>
<term>Glutathione Transferase (genetics)</term>
<term>Glutathione Transferase (metabolism)</term>
<term>Glutathione transferase</term>
<term>Human</term>
<term>Humans</term>
<term>Linkage Disequilibrium</term>
<term>Lod Score</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Molecular biology</term>
<term>Oligonucleotide Array Sequence Analysis</term>
<term>Onset time</term>
<term>Parkinson Disease (enzymology)</term>
<term>Parkinson Disease (genetics)</term>
<term>Parkinson disease</term>
<term>Polymorphism, Single Nucleotide</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Glutathione Transferase</term>
</keywords>
<keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Alzheimer Disease</term>
<term>Parkinson Disease</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Alzheimer Disease</term>
<term>Parkinson Disease</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Glutathione Transferase</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Age of Onset</term>
<term>Aged</term>
<term>Chromosome Mapping</term>
<term>Chromosomes, Human, Pair 10</term>
<term>Female</term>
<term>Humans</term>
<term>Linkage Disequilibrium</term>
<term>Lod Score</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Oligonucleotide Array Sequence Analysis</term>
<term>Polymorphism, Single Nucleotide</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Biologie moléculaire</term>
<term>Démence Alzheimer</term>
<term>Glutathione transferase</term>
<term>Homme</term>
<term>Parkinson maladie</term>
<term>Temps établissement</term>
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<front><div type="abstract" xml:lang="en">We previously reported genetic linkage of loci controlling age-at-onset in Alzheimer disease (AD) and Parkinson's disease (PD) to a 15 cM region on chromosome 10q. Given the large number of genes in this initial starting region, we applied the process of ‘genomic convergence’ to prioritize and reduce the number of candidate genes for further analysis. As our second convergence factor we performed gene expression studies on hippocampus obtained from AD patients and controls. Analysis revealed that four of the genes [stearoyl-CoA desaturase; NADH-ubiquinone oxidoreductase 1 beta subcomplex 8; protease, serine 11; and glutathione S-transferase, omega-1 (GSTO1)] were significantly different in their expression between AD and controls and mapped to the 10q age-at-onset linkage region, the first convergence factor. Using 2814 samples from our AD dataset (1773 AD patients) and 1362 samples from our PD dataset (635 PD patients), allelic association studies for age-at-onset effects in AD and PD revealed no association for three of the candidates, but a significant association was found for GSTO1 (P=0.007) and a second transcribed member of the GST omega class, GSTO2 (P=0.005), located next to GSTO1. The functions of GSTO1 and GSTO2 are not well understood, but recent data suggest that GSTO1 maybe involved in the post-translational modification of the inflammatory cytokine interleukin-1β. This is provocative given reports of the possible role of inflammation in these two neurodegenerative disorders.</div>
</front>
</TEI>
<double idat="0964-6906:2003:Li Y:glutathione:s:transferase"><INIST><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en" level="a">Glutathione S-transferase omega-1 modifies age-at-onset of Alzheimer disease and Parkinson disease</title>
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<s2>Atlanta, GA 30322</s2>
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<s2>Columbus, OH 43210</s2>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Glutathione S-transferase omega-1 modifies age-at-onset of Alzheimer disease and Parkinson disease</title>
<author><name sortKey="Li, Yi Ju" sort="Li, Yi Ju" uniqKey="Li Y" first="Yi" last="Li">Yi Li</name>
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<author><name sortKey="Oliveira, Sofia A" sort="Oliveira, Sofia A" uniqKey="Oliveira S" first="Sofia" last="Oliveira">Sofia Oliveira</name>
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<author><name sortKey="Puting Xu" sort="Puting Xu" uniqKey="Puting Xu" last="Puting">PUTING XU</name>
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<country>États-Unis</country>
<placeName><region type="state">Caroline du Nord</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Martin, Eden R" sort="Martin, Eden R" uniqKey="Martin E" first="Eden" last="Martin">Eden Martin</name>
<affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Medicine and Center for Human Genetics, Duke University Medical Center</s1>
<s2>Durham, NC 27710</s2>
<s3>USA</s3>
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<sZ>2 aut.</sZ>
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</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Caroline du Nord</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Stenger, Judith E" sort="Stenger, Judith E" uniqKey="Stenger J" first="Judith" last="Stenger">Judith Stenger</name>
<affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Medicine and Center for Human Genetics, Duke University Medical Center</s1>
<s2>Durham, NC 27710</s2>
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<country>États-Unis</country>
<placeName><region type="state">Caroline du Nord</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Scherzer, Clemens R" sort="Scherzer, Clemens R" uniqKey="Scherzer C" first="Clemens" last="Scherzer">Clemens Scherzer</name>
<affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Harvard University Medical School</s1>
<s2>Boston, MA 02115</s2>
<s3>USA</s3>
<sZ>6 aut.</sZ>
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</inist:fA14>
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<placeName><region type="state">Massachusetts</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Hauser, Michael A" sort="Hauser, Michael A" uniqKey="Hauser M" first="Michael" last="Hauser">Michael Hauser</name>
<affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Medicine and Center for Human Genetics, Duke University Medical Center</s1>
<s2>Durham, NC 27710</s2>
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<sZ>1 aut.</sZ>
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<country>États-Unis</country>
<placeName><region type="state">Caroline du Nord</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Scott, William K" sort="Scott, William K" uniqKey="Scott W" first="William" last="Scott">William Scott</name>
<affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Medicine and Center for Human Genetics, Duke University Medical Center</s1>
<s2>Durham, NC 27710</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
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</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Caroline du Nord</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Small, Gary W" sort="Small, Gary W" uniqKey="Small G" first="Gary" last="Small">Gary Small</name>
<affiliation wicri:level="2"><inist:fA14 i1="03"><s1>Departments of Psychiatry and Biobehavioral Science and Neurology, University of California</s1>
<s2>Los Angeles, CA 90024</s2>
<s3>USA</s3>
<sZ>9 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
</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"><inist:fA14 i1="04"><s1>Struthers Parkinson Center</s1>
<s2>Golden Valley, MN 55426</s2>
<s3>USA</s3>
<sZ>10 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Minnesota</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Watts, Ray L" sort="Watts, Ray L" uniqKey="Watts R" first="Ray" last="Watts">Ray Watts</name>
<affiliation wicri:level="2"><inist:fA14 i1="05"><s1>Department of Neurology, Emory University School of Medicine</s1>
<s2>Atlanta, GA 30322</s2>
<s3>USA</s3>
<sZ>11 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Géorgie (États-Unis)</region>
</placeName>
</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"><inist:fA14 i1="06"><s1>Department of Neurology, Ohio State University</s1>
<s2>Columbus, OH 43210</s2>
<s3>USA</s3>
<sZ>12 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Ohio</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Koller, William C" sort="Koller, William C" uniqKey="Koller W" first="William" last="Koller">William Koller</name>
<affiliation wicri:level="2"><inist:fA14 i1="07"><s1>Department of Neurology, University of Miami School of Medicine</s1>
<s2>Miami, FL 33124</s2>
<s3>USA</s3>
<sZ>13 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Floride</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Pahwa, Rajesh" sort="Pahwa, Rajesh" uniqKey="Pahwa R" first="Rajesh" last="Pahwa">Rajesh Pahwa</name>
<affiliation wicri:level="2"><inist:fA14 i1="08"><s1>Depantment of Neurology, University of Kansas Medical Center</s1>
<s2>Kansas City, KS 66045</s2>
<s3>USA</s3>
<sZ>14 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Kansas</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Stern, Mathew B" sort="Stern, Mathew B" uniqKey="Stern M" first="Mathew" last="Stern">Mathew Stern</name>
<affiliation wicri:level="2"><inist:fA14 i1="09"><s1>Department of Neurology, University of Pennsylvania Health System</s1>
<s2>Philadelphia, PA 19104</s2>
<s3>USA</s3>
<sZ>15 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Pennsylvanie</region>
</placeName>
</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"><inist:fA14 i1="10"><s1>Department of Neurology, Marshfield Clinic</s1>
<s2>Marshfield, WI 54449</s2>
<s3>USA</s3>
<sZ>16 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Wisconsin</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Jankovic, Joseph" sort="Jankovic, Joseph" uniqKey="Jankovic J" first="Joseph" last="Jankovic">Joseph Jankovic</name>
<affiliation wicri:level="2"><inist:fA14 i1="11"><s1>Department of Neurology, Baylor College of Medicine</s1>
<s2>Houston, TX 77030</s2>
<s3>USA</s3>
<sZ>17 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Texas</region>
</placeName>
<placeName><settlement type="city">Houston</settlement>
<region type="state">Texas</region>
</placeName>
<orgName type="university" n="3">Baylor College of Medicine</orgName>
</affiliation>
</author>
<author><name sortKey="Goetz, Christopher G" sort="Goetz, Christopher G" uniqKey="Goetz C" first="Christopher" last="Goetz">Christopher Goetz</name>
<affiliation wicri:level="2"><inist:fA14 i1="12"><s1>Department of Neurological Sciences, Rush-Presbyterian-St Luke's Hospital</s1>
<s2>Chicago, IL 60612</s2>
<s3>USA</s3>
<sZ>18 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Illinois</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Mastaglia, Frank" sort="Mastaglia, Frank" uniqKey="Mastaglia F" first="Frank" last="Mastaglia">Frank Mastaglia</name>
<affiliation wicri:level="1"><inist:fA14 i1="13"><s1>Centre for Neuromuscular and Neurological Disorders, University of Western Australia</s1>
<s2>Perth, Western Australia 6009</s2>
<s3>AUS</s3>
<sZ>19 aut.</sZ>
</inist:fA14>
<country>Australie</country>
<wicri:noRegion>Perth, Western Australia 6009</wicri:noRegion>
</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"><inist:fA14 i1="14"><s1>GlaxoSmithKline Research and Development</s1>
<s2>Greenford, Middlesex UB6 OHE</s2>
<s3>GBR</s3>
<sZ>20 aut.</sZ>
</inist:fA14>
<country>Royaume-Uni</country>
<wicri:noRegion>GlaxoSmithKline Research and Development</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Roses, Allen D" sort="Roses, Allen D" uniqKey="Roses A" first="Allen" last="Roses">Allen Roses</name>
<affiliation wicri:level="2"><inist:fA14 i1="15"><s1>GlaxoSmithKline Genetics Research Directorate</s1>
<s2>Research Triangle Park, NC</s2>
<s3>USA</s3>
<sZ>21 aut.</sZ>
<sZ>22 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Caroline du Nord</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Saunders, Ann M" sort="Saunders, Ann M" uniqKey="Saunders A" first="Ann" last="Saunders">Ann Saunders</name>
<affiliation wicri:level="2"><inist:fA14 i1="15"><s1>GlaxoSmithKline Genetics Research Directorate</s1>
<s2>Research Triangle Park, NC</s2>
<s3>USA</s3>
<sZ>21 aut.</sZ>
<sZ>22 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Caroline du Nord</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Schmechel, Donald E" sort="Schmechel, Donald E" uniqKey="Schmechel D" first="Donald" last="Schmechel">Donald Schmechel</name>
<affiliation wicri:level="2"><inist:fA14 i1="16"><s1>Deparlment of Medicine and Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center</s1>
<s2>Durham, NC 27710</s2>
<s3>USA</s3>
<sZ>23 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Caroline du Nord</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Gullans, Steven R" sort="Gullans, Steven R" uniqKey="Gullans S" first="Steven" last="Gullans">Steven Gullans</name>
<affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Harvard University Medical School</s1>
<s2>Boston, MA 02115</s2>
<s3>USA</s3>
<sZ>6 aut.</sZ>
<sZ>24 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Massachusetts</region>
</placeName>
</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"><inist:fA14 i1="17"><s1>Program in Human Genetics, Vanderbilt University Medical Center</s1>
<s2>Nashville, TN 37232</s2>
<s3>USA</s3>
<sZ>25 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Tennessee</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Gilbert, John R" sort="Gilbert, John R" uniqKey="Gilbert J" first="John" last="Gilbert">John Gilbert</name>
<affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Medicine and Center for Human Genetics, Duke University Medical Center</s1>
<s2>Durham, NC 27710</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
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</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Caroline du Nord</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Vance, Jeffery M" sort="Vance, Jeffery M" uniqKey="Vance J" first="Jeffery" last="Vance">Jeffery Vance</name>
<affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Medicine and Center for Human Genetics, Duke University Medical Center</s1>
<s2>Durham, NC 27710</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
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<sZ>27 aut.</sZ>
<sZ>28 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Caroline du Nord</region>
</placeName>
</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 wicri:level="2"><inist:fA14 i1="01"><s1>Department of Medicine and Center for Human Genetics, Duke University Medical Center</s1>
<s2>Durham, NC 27710</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
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<sZ>26 aut.</sZ>
<sZ>27 aut.</sZ>
<sZ>28 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Caroline du Nord</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j" type="main">Human molecular genetics : (Print)</title>
<title level="j" type="abbreviated">Hum. mol. genet. : (Print)</title>
<idno type="ISSN">0964-6906</idno>
<imprint><date when="2003">2003</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><title level="j" type="main">Human molecular genetics : (Print)</title>
<title level="j" type="abbreviated">Hum. mol. genet. : (Print)</title>
<idno type="ISSN">0964-6906</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Alzheimer disease</term>
<term>Glutathione transferase</term>
<term>Human</term>
<term>Molecular biology</term>
<term>Onset time</term>
<term>Parkinson disease</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Homme</term>
<term>Biologie moléculaire</term>
<term>Glutathione transferase</term>
<term>Temps établissement</term>
<term>Démence Alzheimer</term>
<term>Parkinson maladie</term>
</keywords>
<keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Homme</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">We previously reported genetic linkage of loci controlling age-at-onset in Alzheimer disease (AD) and Parkinson's disease (PD) to a <sup>15</sup>
cM region on chromosome 10q. Given the large number of genes in this initial starting region, we applied the process of 'genomic convergence' to prioritize and reduce the number of candidate genes for further analysis. As our second convergence factor we performed gene expression studies on hippocampus obtained from AD patients and controls. Analysis revealed that four of the genes [stearoyl-CoA desaturase; NADH-ubiquinone oxidoreductase 1 beta subcomplex 8; protease, serine 11; and glutathione S-transferase, omega-1 (GSTO1)] were significantly different in their expression between AD and controls and mapped to the 10q age-at-onset linkage region, the first convergence factor. Using 2814 samples from our AD dataset (1773 AD patients) and 1362 samples from our PD dataset (635 PD patients), allelic association studies for age-at-onset effects in AD and PD revealed no association for three of the candidates, but a significant association was found for GSTO1 (P=0.007) and a second transcribed member of the GST omega class, GSTO2 (P=0.005), located next to GSTO1. The functions of GSTO1 and GSTO2 are not well understood, but recent data suggest that GSTO1 maybe involved in the post-translational modification of the inflammatory cytokine interleukin-1β. This is provocative given reports of the possible role of inflammation in these two neurodegenerative disorders.</div>
</front>
</TEI>
</INIST>
<ISTEX><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Glutathione S-transferase omega-1 modifies age-at-onset of Alzheimer disease and Parkinson disease</title>
<author><name sortKey="Li, Yi Ju" sort="Li, Yi Ju" uniqKey="Li Y" first="Yi" last="Li">Yi Li</name>
</author>
<author><name sortKey="Oliveira, Sofia A" sort="Oliveira, Sofia A" uniqKey="Oliveira S" first="Sofia" last="Oliveira">Sofia Oliveira</name>
</author>
<author><name sortKey="Xu, Puting" sort="Xu, Puting" uniqKey="Xu P" first="Puting" last="Xu">Puting Xu</name>
</author>
<author><name sortKey="Martin, Eden R" sort="Martin, Eden R" uniqKey="Martin E" first="Eden" last="Martin">Eden Martin</name>
</author>
<author><name sortKey="Stenger, Judith E" sort="Stenger, Judith E" uniqKey="Stenger J" first="Judith" last="Stenger">Judith Stenger</name>
</author>
<author><name sortKey="Scherzer, Clemens R" sort="Scherzer, Clemens R" uniqKey="Scherzer C" first="Clemens" last="Scherzer">Clemens Scherzer</name>
</author>
<author><name sortKey="Hauser, Michael A" sort="Hauser, Michael A" uniqKey="Hauser M" first="Michael" last="Hauser">Michael Hauser</name>
</author>
<author><name sortKey="Scott, William K" sort="Scott, William K" uniqKey="Scott W" first="William" last="Scott">William Scott</name>
</author>
<author><name sortKey="Small, Gary W" sort="Small, Gary W" uniqKey="Small G" first="Gary" last="Small">Gary Small</name>
</author>
<author><name sortKey="Nance, Martha A" sort="Nance, Martha A" uniqKey="Nance M" first="Martha" last="Nance">Martha Nance</name>
</author>
<author><name sortKey="Watts, Ray L" sort="Watts, Ray L" uniqKey="Watts R" first="Ray" last="Watts">Ray Watts</name>
</author>
<author><name sortKey="Hubble, Jean P" sort="Hubble, Jean P" uniqKey="Hubble J" first="Jean" last="Hubble">Jean Hubble</name>
</author>
<author><name sortKey="Koller, William C" sort="Koller, William C" uniqKey="Koller W" first="William" last="Koller">William Koller</name>
</author>
<author><name sortKey="Pahwa, Rajesh" sort="Pahwa, Rajesh" uniqKey="Pahwa R" first="Rajesh" last="Pahwa">Rajesh Pahwa</name>
</author>
<author><name sortKey="Stern, Mathew B" sort="Stern, Mathew B" uniqKey="Stern M" first="Mathew" last="Stern">Mathew Stern</name>
</author>
<author><name sortKey="Hiner, Bradley C" sort="Hiner, Bradley C" uniqKey="Hiner B" first="Bradley" last="Hiner">Bradley Hiner</name>
</author>
<author><name sortKey="Jankovic, Joseph" sort="Jankovic, Joseph" uniqKey="Jankovic J" first="Joseph" last="Jankovic">Joseph Jankovic</name>
<affiliation><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>
</author>
<author><name sortKey="Goetz, Christopher G" sort="Goetz, Christopher G" uniqKey="Goetz C" first="Christopher" last="Goetz">Christopher Goetz</name>
</author>
<author><name sortKey="Mastaglia, Frank" sort="Mastaglia, Frank" uniqKey="Mastaglia F" first="Frank" last="Mastaglia">Frank Mastaglia</name>
</author>
<author><name sortKey="Middleton, Lefkos T" sort="Middleton, Lefkos T" uniqKey="Middleton L" first="Lefkos" last="Middleton">Lefkos Middleton</name>
</author>
<author><name sortKey="Roses, Allen D" sort="Roses, Allen D" uniqKey="Roses A" first="Allen" last="Roses">Allen Roses</name>
</author>
<author><name sortKey="Saunders, Ann M" sort="Saunders, Ann M" uniqKey="Saunders A" first="Ann" last="Saunders">Ann Saunders</name>
</author>
<author><name sortKey="Schmechel, Donald E" sort="Schmechel, Donald E" uniqKey="Schmechel D" first="Donald" last="Schmechel">Donald Schmechel</name>
</author>
<author><name sortKey="Gullans, Steven R" sort="Gullans, Steven R" uniqKey="Gullans S" first="Steven" last="Gullans">Steven Gullans</name>
</author>
<author><name sortKey="Haines, Jonathan L" sort="Haines, Jonathan L" uniqKey="Haines J" first="Jonathan" last="Haines">Jonathan Haines</name>
</author>
<author><name sortKey="Gilbert, John R" sort="Gilbert, John R" uniqKey="Gilbert J" first="John" last="Gilbert">John Gilbert</name>
</author>
<author><name sortKey="Vance, Jeffery M" sort="Vance, Jeffery M" uniqKey="Vance J" first="Jeffery" last="Vance">Jeffery Vance</name>
</author>
<author><name sortKey="Pericak Vance, Margaret A" sort="Pericak Vance, Margaret A" uniqKey="Pericak Vance M" first="Margaret" last="Pericak">Margaret Pericak</name>
</author>
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<sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Glutathione S-transferase omega-1 modifies age-at-onset of Alzheimer disease and Parkinson disease</title>
<author><name sortKey="Li, Yi Ju" sort="Li, Yi Ju" uniqKey="Li Y" first="Yi" last="Li">Yi Li</name>
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<author><name sortKey="Oliveira, Sofia A" sort="Oliveira, Sofia A" uniqKey="Oliveira S" first="Sofia" last="Oliveira">Sofia Oliveira</name>
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<author><name sortKey="Xu, Puting" sort="Xu, Puting" uniqKey="Xu P" first="Puting" last="Xu">Puting Xu</name>
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<author><name sortKey="Martin, Eden R" sort="Martin, Eden R" uniqKey="Martin E" first="Eden" last="Martin">Eden Martin</name>
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<author><name sortKey="Scherzer, Clemens R" sort="Scherzer, Clemens R" uniqKey="Scherzer C" first="Clemens" last="Scherzer">Clemens Scherzer</name>
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</affiliation>
</author>
<author><name sortKey="Nance, Martha A" sort="Nance, Martha A" uniqKey="Nance M" first="Martha" last="Nance">Martha Nance</name>
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</affiliation>
</author>
<author><name sortKey="Hubble, Jean P" sort="Hubble, Jean P" uniqKey="Hubble J" first="Jean" last="Hubble">Jean Hubble</name>
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</affiliation>
</author>
<author><name sortKey="Koller, William C" sort="Koller, William C" uniqKey="Koller W" first="William" last="Koller">William Koller</name>
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</affiliation>
</author>
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</affiliation>
</author>
<author><name sortKey="Stern, Mathew B" sort="Stern, Mathew B" uniqKey="Stern M" first="Mathew" last="Stern">Mathew Stern</name>
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</affiliation>
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</affiliation>
</author>
<author><name sortKey="Jankovic, Joseph" sort="Jankovic, Joseph" uniqKey="Jankovic J" first="Joseph" last="Jankovic">Joseph Jankovic</name>
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<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>
</author>
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</affiliation>
</author>
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</affiliation>
</author>
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</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"><country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Program in Human Genetics, Vanderbilt University Medical Center, Nashville, TN 37232</wicri:regionArea>
<placeName><region type="state">Tennessee</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Gilbert, John R" sort="Gilbert, John R" uniqKey="Gilbert J" first="John" last="Gilbert">John Gilbert</name>
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</affiliation>
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</affiliation>
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<author><name sortKey="Pericak Vance, Margaret A" sort="Pericak Vance, Margaret A" uniqKey="Pericak Vance M" first="Margaret" last="Pericak">Margaret Pericak</name>
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</affiliation>
</author>
</analytic>
<monogr></monogr>
<series><title level="j">Human Molecular Genetics</title>
<title level="j" type="abbrev">Hum. Mol. Genet.</title>
<idno type="ISSN">0964-6906</idno>
<idno type="eISSN">1460-2083</idno>
<imprint><publisher>Oxford University Press</publisher>
<date type="published" when="2003-12-15">2003-12-15</date>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Age of Onset</term>
<term>Aged</term>
<term>Alzheimer Disease (enzymology)</term>
<term>Alzheimer Disease (genetics)</term>
<term>Chromosome Mapping</term>
<term>Chromosomes, Human, Pair 10</term>
<term>Female</term>
<term>Glutathione Transferase (genetics)</term>
<term>Glutathione Transferase (metabolism)</term>
<term>Humans</term>
<term>Linkage Disequilibrium</term>
<term>Lod Score</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Oligonucleotide Array Sequence Analysis</term>
<term>Parkinson Disease (enzymology)</term>
<term>Parkinson Disease (genetics)</term>
<term>Polymorphism, Single Nucleotide</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Glutathione Transferase</term>
</keywords>
<keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Alzheimer Disease</term>
<term>Parkinson Disease</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Alzheimer Disease</term>
<term>Parkinson Disease</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Glutathione Transferase</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Age of Onset</term>
<term>Aged</term>
<term>Chromosome Mapping</term>
<term>Chromosomes, Human, Pair 10</term>
<term>Female</term>
<term>Humans</term>
<term>Linkage Disequilibrium</term>
<term>Lod Score</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Oligonucleotide Array Sequence Analysis</term>
<term>Polymorphism, Single Nucleotide</term>
</keywords>
</textClass>
<langUsage><language ident="en">en</language>
</langUsage>
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</teiHeader>
<front><div type="abstract" xml:lang="en">We previously reported genetic linkage of loci controlling age-at-onset in Alzheimer disease (AD) and Parkinson's disease (PD) to a 15 cM region on chromosome 10q. Given the large number of genes in this initial starting region, we applied the process of ‘genomic convergence’ to prioritize and reduce the number of candidate genes for further analysis. As our second convergence factor we performed gene expression studies on hippocampus obtained from AD patients and controls. Analysis revealed that four of the genes [stearoyl-CoA desaturase; NADH-ubiquinone oxidoreductase 1 beta subcomplex 8; protease, serine 11; and glutathione S-transferase, omega-1 (GSTO1)] were significantly different in their expression between AD and controls and mapped to the 10q age-at-onset linkage region, the first convergence factor. Using 2814 samples from our AD dataset (1773 AD patients) and 1362 samples from our PD dataset (635 PD patients), allelic association studies for age-at-onset effects in AD and PD revealed no association for three of the candidates, but a significant association was found for GSTO1 (P=0.007) and a second transcribed member of the GST omega class, GSTO2 (P=0.005), located next to GSTO1. The functions of GSTO1 and GSTO2 are not well understood, but recent data suggest that GSTO1 maybe involved in the post-translational modification of the inflammatory cytokine interleukin-1β. This is provocative given reports of the possible role of inflammation in these two neurodegenerative disorders.</div>
</front>
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