Glutathione S-transferase omega-1 modifies age-at-onset of Alzheimer disease and Parkinson disease
Identifieur interne : 000063 ( PascalFrancis/Curation ); précédent : 000062; suivant : 000064Glutathione S-transferase omega-1 modifies age-at-onset of Alzheimer disease and Parkinson disease
Auteurs : Yi Li [États-Unis] ; Sofia Oliveira [États-Unis] ; PUTING XU [États-Unis] ; Eden Martin [États-Unis] ; Judith Stenger [États-Unis] ; Clemens Scherzer [États-Unis] ; Michael Hauser [États-Unis] ; William Scott [États-Unis] ; Gary Small [États-Unis] ; Martha Nance [États-Unis] ; Ray Watts [États-Unis] ; Jean Hubble [États-Unis] ; William Koller [États-Unis] ; Rajesh Pahwa [États-Unis] ; Mathew Stern [États-Unis] ; Bradley Hiner [États-Unis] ; Joseph Jankovic [États-Unis] ; Christopher Goetz [États-Unis] ; Frank Mastaglia [Australie] ; Lefkos Middleton [Royaume-Uni] ; Allen Roses [États-Unis] ; Ann Saunders [États-Unis] ; Donald Schmechel [États-Unis] ; Steven Gullans [États-Unis] ; Jonathan Haines [États-Unis] ; John Gilbert [États-Unis] ; Jeffery Vance [États-Unis] ; Margaret Pericak [États-Unis]Source :
- Human molecular genetics : (Print) [ 0964-6906 ] ; 2003.
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Abstract
We previously reported genetic linkage of loci controlling age-at-onset in Alzheimer disease (AD) and Parkinson's disease (PD) to a 15cM 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.
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27710</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ><sZ>28 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Puting Xu" sort="Puting Xu" uniqKey="Puting Xu" last="Puting">PUTING XU</name><affiliation wicri:level="1"><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><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ><sZ>28 aut.</sZ></inist:fA14><country>États-Unis</country></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="1"><inist:fA14 i1="01"><s1>Department of Medicine and Center for Human Genetics, Duke University Medical 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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></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="1"><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><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ><sZ>28 aut.</sZ></inist:fA14><country>États-Unis</country></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="1"><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><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ><sZ>28 aut.</sZ></inist:fA14><country>États-Unis</country></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="1"><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></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="1"><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></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="1"><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></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="1"><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></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="1"><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></affiliation></author><author><name sortKey="Pahwa, Rajesh" sort="Pahwa, Rajesh" uniqKey="Pahwa R" first="Rajesh" last="Pahwa">Rajesh Pahwa</name><affiliation wicri:level="1"><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></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="1"><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></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="1"><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></affiliation></author><author><name sortKey="Jankovic, Joseph" sort="Jankovic, Joseph" uniqKey="Jankovic J" first="Joseph" last="Jankovic">Joseph Jankovic</name><affiliation wicri:level="1"><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></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="1"><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></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></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></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="1"><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></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="1"><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></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="1"><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></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="1"><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></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="1"><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></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="1"><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><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ><sZ>28 aut.</sZ></inist:fA14><country>États-Unis</country></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="1"><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><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ><sZ>28 aut.</sZ></inist:fA14><country>États-Unis</country></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="1"><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><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ><sZ>28 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">04-0080689</idno><date when="2003">2003</date><idno type="stanalyst">PASCAL 04-0080689 INIST</idno><idno type="RBID">Pascal:04-0080689</idno><idno type="wicri:Area/PascalFrancis/Corpus">000103</idno><idno type="wicri:Area/PascalFrancis/Curation">000063</idno></publicationStmt><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><affiliation wicri:level="1"><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><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ><sZ>28 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Oliveira, Sofia A" sort="Oliveira, Sofia A" uniqKey="Oliveira S" first="Sofia" last="Oliveira">Sofia Oliveira</name><affiliation wicri:level="1"><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><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ><sZ>28 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Puting Xu" sort="Puting Xu" uniqKey="Puting Xu" last="Puting">PUTING XU</name><affiliation wicri:level="1"><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><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ><sZ>28 aut.</sZ></inist:fA14><country>États-Unis</country></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="1"><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><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ><sZ>28 aut.</sZ></inist:fA14><country>États-Unis</country></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="1"><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><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ><sZ>28 aut.</sZ></inist:fA14><country>États-Unis</country></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="1"><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></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="1"><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><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ><sZ>28 aut.</sZ></inist:fA14><country>États-Unis</country></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="1"><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><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ><sZ>28 aut.</sZ></inist:fA14><country>États-Unis</country></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="1"><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></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="1"><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></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="1"><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></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="1"><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></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="1"><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></affiliation></author><author><name sortKey="Pahwa, Rajesh" sort="Pahwa, Rajesh" uniqKey="Pahwa R" first="Rajesh" last="Pahwa">Rajesh Pahwa</name><affiliation wicri:level="1"><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></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="1"><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></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="1"><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></affiliation></author><author><name sortKey="Jankovic, Joseph" sort="Jankovic, Joseph" uniqKey="Jankovic J" first="Joseph" last="Jankovic">Joseph Jankovic</name><affiliation wicri:level="1"><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></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="1"><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></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></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></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="1"><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></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="1"><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></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="1"><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></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="1"><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></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="1"><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></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="1"><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><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ><sZ>28 aut.</sZ></inist:fA14><country>États-Unis</country></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="1"><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><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ><sZ>28 aut.</sZ></inist:fA14><country>États-Unis</country></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="1"><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><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ><sZ>28 aut.</sZ></inist:fA14><country>États-Unis</country></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><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0964-6906</s0></fA01><fA03 i2="1"><s0>Hum. mol. genet. : (Print)</s0></fA03><fA05><s2>12</s2></fA05><fA06><s2>24</s2></fA06><fA08 i1="01" i2="1" l="ENG"><s1>Glutathione S-transferase omega-1 modifies age-at-onset of Alzheimer disease and Parkinson disease</s1></fA08><fA11 i1="01" i2="1"><s1>LI (Yi-Ju)</s1></fA11><fA11 i1="02" i2="1"><s1>OLIVEIRA (Sofia A.)</s1></fA11><fA11 i1="03" i2="1"><s1>PUTING XU</s1></fA11><fA11 i1="04" i2="1"><s1>MARTIN (Eden R.)</s1></fA11><fA11 i1="05" i2="1"><s1>STENGER (Judith E.)</s1></fA11><fA11 i1="06" i2="1"><s1>SCHERZER (Clemens R.)</s1></fA11><fA11 i1="07" i2="1"><s1>HAUSER (Michael A.)</s1></fA11><fA11 i1="08" i2="1"><s1>SCOTT (William K.)</s1></fA11><fA11 i1="09" i2="1"><s1>SMALL (Gary W.)</s1></fA11><fA11 i1="10" i2="1"><s1>NANCE (Martha A.)</s1></fA11><fA11 i1="11" i2="1"><s1>WATTS (Ray L.)</s1></fA11><fA11 i1="12" i2="1"><s1>HUBBLE (Jean P.)</s1></fA11><fA11 i1="13" i2="1"><s1>KOLLER (William C.)</s1></fA11><fA11 i1="14" i2="1"><s1>PAHWA (Rajesh)</s1></fA11><fA11 i1="15" i2="1"><s1>STERN (Mathew B.)</s1></fA11><fA11 i1="16" i2="1"><s1>HINER (Bradley C.)</s1></fA11><fA11 i1="17" i2="1"><s1>JANKOVIC (Joseph)</s1></fA11><fA11 i1="18" i2="1"><s1>GOETZ (Christopher G.)</s1></fA11><fA11 i1="19" i2="1"><s1>MASTAGLIA (Frank)</s1></fA11><fA11 i1="20" i2="1"><s1>MIDDLETON (Lefkos T.)</s1></fA11><fA11 i1="21" i2="1"><s1>ROSES (Allen D.)</s1></fA11><fA11 i1="22" i2="1"><s1>SAUNDERS (Ann M.)</s1></fA11><fA11 i1="23" i2="1"><s1>SCHMECHEL (Donald E.)</s1></fA11><fA11 i1="24" i2="1"><s1>GULLANS (Steven R.)</s1></fA11><fA11 i1="25" i2="1"><s1>HAINES (Jonathan L.)</s1></fA11><fA11 i1="26" i2="1"><s1>GILBERT (John R.)</s1></fA11><fA11 i1="27" i2="1"><s1>VANCE (Jeffery M.)</s1></fA11><fA11 i1="28" i2="1"><s1>PERICAK-VANCE (Margaret A.)</s1></fA11><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><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ><sZ>28 aut.</sZ></fA14><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></fA14><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></fA14><fA14 i1="04"><s1>Struthers Parkinson Center</s1><s2>Golden Valley, MN 55426</s2><s3>USA</s3><sZ>10 aut.</sZ></fA14><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></fA14><fA14 i1="06"><s1>Department of Neurology, Ohio State University</s1><s2>Columbus, OH 43210</s2><s3>USA</s3><sZ>12 aut.</sZ></fA14><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></fA14><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></fA14><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></fA14><fA14 i1="10"><s1>Department of Neurology, Marshfield Clinic</s1><s2>Marshfield, WI 54449</s2><s3>USA</s3><sZ>16 aut.</sZ></fA14><fA14 i1="11"><s1>Department of Neurology, Baylor College of Medicine</s1><s2>Houston, TX 77030</s2><s3>USA</s3><sZ>17 aut.</sZ></fA14><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></fA14><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></fA14><fA14 i1="14"><s1>GlaxoSmithKline Research and Development</s1><s2>Greenford, Middlesex UB6 OHE</s2><s3>GBR</s3><sZ>20 aut.</sZ></fA14><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></fA14><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></fA14><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></fA14><fA20><s1>3259-3267</s1></fA20><fA21><s1>2003</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>22540</s2><s5>354000116106730060</s5></fA43><fA44><s0>0000</s0><s1>© 2004 INIST-CNRS. All rights reserved.</s1></fA44><fA45><s0>33 ref.</s0></fA45><fA47 i1="01" i2="1"><s0>04-0080689</s0></fA47><fA60><s1>P</s1></fA60><fA61><s0>A</s0></fA61><fA64 i1="01" i2="1"><s0>Human molecular genetics : (Print)</s0></fA64><fA66 i1="01"><s0>GBR</s0></fA66><fC01 i1="01" l="ENG"><s0>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.</s0></fC01><fC02 i1="01" i2="X"><s0>002A07C03</s0></fC02><fC03 i1="01" i2="X" l="FRE"><s0>Homme</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="ENG"><s0>Human</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="SPA"><s0>Hombre</s0><s5>01</s5></fC03><fC03 i1="02" i2="X" l="FRE"><s0>Biologie moléculaire</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="ENG"><s0>Molecular biology</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="SPA"><s0>Biología molecular</s0><s5>02</s5></fC03><fC03 i1="03" i2="X" l="FRE"><s0>Glutathione transferase</s0><s2>FE</s2><s5>03</s5></fC03><fC03 i1="03" i2="X" l="ENG"><s0>Glutathione transferase</s0><s2>FE</s2><s5>03</s5></fC03><fC03 i1="03" i2="X" l="SPA"><s0>Glutathione transferase</s0><s2>FE</s2><s5>03</s5></fC03><fC03 i1="04" i2="X" l="FRE"><s0>Temps établissement</s0><s5>04</s5></fC03><fC03 i1="04" i2="X" l="ENG"><s0>Onset time</s0><s5>04</s5></fC03><fC03 i1="04" i2="X" l="SPA"><s0>Tiempo establecimiento</s0><s5>04</s5></fC03><fC03 i1="05" i2="X" l="FRE"><s0>Démence Alzheimer</s0><s5>14</s5></fC03><fC03 i1="05" i2="X" l="ENG"><s0>Alzheimer disease</s0><s5>14</s5></fC03><fC03 i1="05" i2="X" l="SPA"><s0>Demencia Alzheimer</s0><s5>14</s5></fC03><fC03 i1="06" i2="X" l="FRE"><s0>Parkinson maladie</s0><s5>15</s5></fC03><fC03 i1="06" i2="X" l="ENG"><s0>Parkinson disease</s0><s5>15</s5></fC03><fC03 i1="06" i2="X" l="SPA"><s0>Parkinson enfermedad</s0><s5>15</s5></fC03><fC07 i1="01" i2="X" l="FRE"><s0>Transferases</s0><s2>FE</s2></fC07><fC07 i1="01" i2="X" l="ENG"><s0>Transferases</s0><s2>FE</s2></fC07><fC07 i1="01" i2="X" l="SPA"><s0>Transferases</s0><s2>FE</s2></fC07><fC07 i1="02" i2="X" l="FRE"><s0>Enzyme</s0><s2>FE</s2></fC07><fC07 i1="02" i2="X" l="ENG"><s0>Enzyme</s0><s2>FE</s2></fC07><fC07 i1="02" i2="X" l="SPA"><s0>Enzima</s0><s2>FE</s2></fC07><fN21><s1>054</s1></fN21><fN82><s1>PSI</s1></fN82></pA></standard></inist></record>Pour manipuler ce document sous Unix (Dilib)
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