Two sites in the MAPT region confer genetic risk for Guam ALS/PDC and dementia
Identifieur interne : 001E11 ( Main/Corpus ); précédent : 001E10; suivant : 001E12Two sites in the MAPT region confer genetic risk for Guam ALS/PDC and dementia
Auteurs : Purnima Desai Sundar ; Chang-En Yu ; Weiva Sieh ; Ellen Steinbart ; Ralph M. Garruto ; Kiyomitsu Oyanagi ; Ulla-Katrina Craig ; Thomas D. Bird ; Ellen M. Wijsman ; Douglas R. Galasko ; Gerard D. SchellenbergSource :
- Human Molecular Genetics [ 0964-6906 ] ; 2007-02-01.
Abstract
Unusual forms of amyotrophic lateral sclerosis (ALS-G), Parkinsonism dementia complex (PDC-G) and Guam dementia (GD) are found in Chamorros, the indigenous people of Guam. Neurofibrillary tangles composed of hyperphosphorylated tau are a neuropathologic feature of these closely related disorders. To determine if variation in the gene that encodes microtubule-associated protein tau gene (MAPT) contributes to risk for these disorders, we genotyped nine single nucleotide polymorphism (SNP) sites and one insertion/deletion in the 5 end of MAPT in 54 ALS-G, 135 PDC-G, 153 GD and 258 control subjects, all of whom are Chamorros. Variation at three SNPs (sites 2, 6 and 9) influenced risk for ALS-G, PDC-G and GD. SNP2 acts through a dominant mechanism and is independent of the risk conferred by SNPs 6 and 9, the latter two acting by a recessive mechanism. Persons with the high-risk SNP6 and SNP9 AC/AC diplotype had an increased risk of 3-fold [95 confidence interval (CI)1.108.25] for GD, 4-fold (95 CI1.4011.64) for PDC-G and 6-fold (95 CI1.4432.14) for ALS-G, compared to persons with other diplotypes after adjusting for SNP2. Carriers of the SNP2 G allele had an increased risk of 1.6-fold (95 CI1.002.62) for GD, 2-fold (95 CI1.283.66) for PDC-G, and 1.5-fold (95 CI0.743.00) for ALS-G, compared to non-carriers after adjusting for SNPs 6 and 9. Others have shown that SNP6 is also associated with risk for progressive supranuclear palsy. These two independent cis-acting sites presumably influence risk for Guam neuro-degenerative disorders by regulating MAPT expression.
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DOI: 10.1093/hmg/ddl463
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Schellenberg</name><affiliation><mods:affiliation></mods:affiliation></affiliation><affiliation><mods:affiliation></mods:affiliation></affiliation><affiliation><mods:affiliation></mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: zachdad@u.washington.edu</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Human Molecular Genetics</title><idno type="ISSN">0964-6906</idno><idno type="eISSN">1460-2083</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2007-02-01">2007-02-01</date><biblScope unit="volume">16</biblScope><biblScope unit="issue">3</biblScope><biblScope unit="page" from="295">295</biblScope><biblScope unit="page" to="306">306</biblScope></imprint><idno type="ISSN">0964-6906</idno></series><idno type="istex">2C3AD66B511CAEDC5F43F85522DAEA593774CDF3</idno><idno type="DOI">10.1093/hmg/ddl463</idno><idno type="ArticleID">ddl463</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0964-6906</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract">Unusual forms of amyotrophic lateral sclerosis (ALS-G), Parkinsonism dementia complex (PDC-G) and Guam dementia (GD) are found in Chamorros, the indigenous people of Guam. Neurofibrillary tangles composed of hyperphosphorylated tau are a neuropathologic feature of these closely related disorders. To determine if variation in the gene that encodes microtubule-associated protein tau gene (MAPT) contributes to risk for these disorders, we genotyped nine single nucleotide polymorphism (SNP) sites and one insertion/deletion in the 5 end of MAPT in 54 ALS-G, 135 PDC-G, 153 GD and 258 control subjects, all of whom are Chamorros. Variation at three SNPs (sites 2, 6 and 9) influenced risk for ALS-G, PDC-G and GD. SNP2 acts through a dominant mechanism and is independent of the risk conferred by SNPs 6 and 9, the latter two acting by a recessive mechanism. Persons with the high-risk SNP6 and SNP9 AC/AC diplotype had an increased risk of 3-fold [95 confidence interval (CI)1.108.25] for GD, 4-fold (95 CI1.4011.64) for PDC-G and 6-fold (95 CI1.4432.14) for ALS-G, compared to persons with other diplotypes after adjusting for SNP2. Carriers of the SNP2 G allele had an increased risk of 1.6-fold (95 CI1.002.62) for GD, 2-fold (95 CI1.283.66) for PDC-G, and 1.5-fold (95 CI0.743.00) for ALS-G, compared to non-carriers after adjusting for SNPs 6 and 9. Others have shown that SNP6 is also associated with risk for progressive supranuclear palsy. These two independent cis-acting sites presumably influence risk for Guam neuro-degenerative disorders by regulating MAPT expression.</div></front></TEI><istex><corpusName>oup</corpusName><author><json:item><name>Purnima Desai Sundar</name><affiliations><json:string>Department of Medicine, Division of Gerontology and Geriatric Medicine,</json:string><json:string>Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle Division, Seattle, WA 98108, USA,</json:string></affiliations></json:item><json:item><name>Chang-En Yu</name><affiliations><json:string>Department of Medicine, Division of Gerontology and Geriatric Medicine,</json:string><json:string>Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle Division, Seattle, WA 98108, USA,</json:string></affiliations></json:item><json:item><name>Weiva Sieh</name><affiliations><json:string>Department of Medicine, Division of Medical Genetics,</json:string></affiliations></json:item><json:item><name>Ellen Steinbart</name><affiliations><json:string>Department of Medicine, Division of Gerontology and Geriatric Medicine,</json:string><json:string>Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle Division, Seattle, WA 98108, USA,</json:string></affiliations></json:item><json:item><name>Ralph M. Garruto</name><affiliations><json:string>Department of Anthropology, Laboratory of Biomedical Anthropology and Neurosciences, Binghamton University, SUNY-Binghamton, NY 13902-6000, USA,</json:string></affiliations></json:item><json:item><name>Kiyomitsu Oyanagi</name><affiliations><json:string>Department of Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Tokyo, Japan,</json:string></affiliations></json:item><json:item><name>Ulla-Katrina Craig</name><affiliations><json:string>University of Guam, Mangilao, Guam 96923, USA and</json:string></affiliations></json:item><json:item><name>Thomas D. Bird</name><affiliations><json:string>Department of Neurology and Pharmacology, University of Washington, Seattle, WA 98195, USA,</json:string><json:string>Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle Division, Seattle, WA 98108, USA,</json:string></affiliations></json:item><json:item><name>Ellen M. Wijsman</name><affiliations><json:string>Department of Medicine, Division of Medical Genetics,</json:string><json:string>Department of Biostatistics,</json:string></affiliations></json:item><json:item><name>Douglas R. Galasko</name><affiliations><json:string>Department of Neurosciences, University of California, San Diego, La Jolla CA 92093-0662, USA</json:string></affiliations></json:item><json:item><name>Gerard D. Schellenberg</name><affiliations><json:string>Department of Medicine, Division of Gerontology and Geriatric Medicine,</json:string><json:string>Department of Neurology and Pharmacology, University of Washington, Seattle, WA 98195, USA,</json:string><json:string>Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle Division, Seattle, WA 98108, USA,</json:string><json:string>E-mail: zachdad@u.washington.edu</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>ARTICLES</value></json:item></subject><language><json:string>eng</json:string></language><abstract>Unusual forms of amyotrophic lateral sclerosis (ALS-G), Parkinsonism dementia complex (PDC-G) and Guam dementia (GD) are found in Chamorros, the indigenous people of Guam. Neurofibrillary tangles composed of hyperphosphorylated tau are a neuropathologic feature of these closely related disorders. To determine if variation in the gene that encodes microtubule-associated protein tau gene (MAPT) contributes to risk for these disorders, we genotyped nine single nucleotide polymorphism (SNP) sites and one insertion/deletion in the 5 end of MAPT in 54 ALS-G, 135 PDC-G, 153 GD and 258 control subjects, all of whom are Chamorros. Variation at three SNPs (sites 2, 6 and 9) influenced risk for ALS-G, PDC-G and GD. SNP2 acts through a dominant mechanism and is independent of the risk conferred by SNPs 6 and 9, the latter two acting by a recessive mechanism. Persons with the high-risk SNP6 and SNP9 AC/AC diplotype had an increased risk of 3-fold [95 confidence interval (CI)1.108.25] for GD, 4-fold (95 CI1.4011.64) for PDC-G and 6-fold (95 CI1.4432.14) for ALS-G, compared to persons with other diplotypes after adjusting for SNP2. Carriers of the SNP2 G allele had an increased risk of 1.6-fold (95 CI1.002.62) for GD, 2-fold (95 CI1.283.66) for PDC-G, and 1.5-fold (95 CI0.743.00) for ALS-G, compared to non-carriers after adjusting for SNPs 6 and 9. Others have shown that SNP6 is also associated with risk for progressive supranuclear palsy. These two independent cis-acting sites presumably influence risk for Guam neuro-degenerative disorders by regulating MAPT expression.</abstract><qualityIndicators><score>7.916</score><pdfVersion>1.2</pdfVersion><pdfPageSize>610 x 795 pts</pdfPageSize><refBibsNative>false</refBibsNative><keywordCount>1</keywordCount><abstractCharCount>1582</abstractCharCount><pdfWordCount>8203</pdfWordCount><pdfCharCount>52465</pdfCharCount><pdfPageCount>12</pdfPageCount><abstractWordCount>243</abstractWordCount></qualityIndicators><title>Two sites in the MAPT region confer genetic risk for Guam ALS/PDC and dementia</title><genre><json:string>research-article</json:string></genre><host><volume>16</volume><pages><last>306</last><first>295</first></pages><issn><json:string>0964-6906</json:string></issn><issue>3</issue><genre></genre><language><json:string>unknown</json:string></language><eissn><json:string>1460-2083</json:string></eissn><title>Human Molecular 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ident="en">en</language></langUsage><abstract><p>Unusual forms of amyotrophic lateral sclerosis (ALS-G), Parkinsonism dementia complex (PDC-G) and Guam dementia (GD) are found in Chamorros, the indigenous people of Guam. Neurofibrillary tangles composed of hyperphosphorylated tau are a neuropathologic feature of these closely related disorders. To determine if variation in the gene that encodes microtubule-associated protein tau gene (MAPT) contributes to risk for these disorders, we genotyped nine single nucleotide polymorphism (SNP) sites and one insertion/deletion in the 5 end of MAPT in 54 ALS-G, 135 PDC-G, 153 GD and 258 control subjects, all of whom are Chamorros. Variation at three SNPs (sites 2, 6 and 9) influenced risk for ALS-G, PDC-G and GD. SNP2 acts through a dominant mechanism and is independent of the risk conferred by SNPs 6 and 9, the latter two acting by a recessive mechanism. Persons with the high-risk SNP6 and SNP9 AC/AC diplotype had an increased risk of 3-fold [95 confidence interval (CI)1.108.25] for GD, 4-fold (95 CI1.4011.64) for PDC-G and 6-fold (95 CI1.4432.14) for ALS-G, compared to persons with other diplotypes after adjusting for SNP2. Carriers of the SNP2 G allele had an increased risk of 1.6-fold (95 CI1.002.62) for GD, 2-fold (95 CI1.283.66) for PDC-G, and 1.5-fold (95 CI0.743.00) for ALS-G, compared to non-carriers after adjusting for SNPs 6 and 9. Others have shown that SNP6 is also associated with risk for progressive supranuclear palsy. 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name="istex:docType"></istex:docType><istex:document><article article-type="research-article"><front><journal-meta><journal-id journal-id-type="hwp">hmg</journal-id><journal-id journal-id-type="publisher-id">hmg</journal-id><journal-title>Human Molecular Genetics</journal-title><issn pub-type="ppub">0964-6906</issn><issn pub-type="epub">1460-2083</issn><publisher><publisher-name>Oxford University Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.1093/hmg/ddl463</article-id><article-id pub-id-type="publisher-id">ddl463</article-id><article-categories><subj-group><subject>ARTICLES</subject></subj-group></article-categories><title-group><article-title>Two sites in the <italic>MAPT</italic> region confer genetic risk for Guam ALS/PDC and dementia</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Sundar</surname><given-names>Purnima Desai</given-names></name><xref ref-type="aff" rid="af1">1</xref><xref ref-type="aff" rid="af5">5</xref></contrib><contrib contrib-type="author"><name><surname>Yu</surname><given-names>Chang-En</given-names></name><xref ref-type="aff" rid="af1">1</xref><xref ref-type="aff" rid="af5">5</xref></contrib><contrib contrib-type="author"><name><surname>Sieh</surname><given-names>Weiva</given-names></name><xref ref-type="aff" rid="af2">2</xref></contrib><contrib contrib-type="author"><name><surname>Steinbart</surname><given-names>Ellen</given-names></name><xref ref-type="aff" rid="af1">1</xref><xref ref-type="aff" rid="af5">5</xref></contrib><contrib contrib-type="author"><name><surname>Garruto</surname><given-names>Ralph M.</given-names></name><xref ref-type="aff" rid="af6">6</xref></contrib><contrib contrib-type="author"><name><surname>Oyanagi</surname><given-names>Kiyomitsu</given-names></name><xref ref-type="aff" rid="af7">7</xref></contrib><contrib contrib-type="author"><name><surname>Craig</surname><given-names>Ulla-Katrina</given-names></name><xref ref-type="aff" rid="af8">8</xref></contrib><contrib contrib-type="author"><name><surname>Bird</surname><given-names>Thomas D.</given-names></name><xref ref-type="aff" rid="af4">4</xref><xref ref-type="aff" rid="af5">5</xref></contrib><contrib contrib-type="author"><name><surname>Wijsman</surname><given-names>Ellen M.</given-names></name><xref ref-type="aff" rid="af2">2</xref><xref ref-type="aff" rid="af3">3</xref></contrib><contrib contrib-type="author"><name><surname>Galasko</surname><given-names>Douglas R.</given-names></name><xref ref-type="aff" rid="af9">9</xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Schellenberg</surname><given-names>Gerard D.</given-names></name><xref ref-type="aff" rid="af1">1</xref><xref ref-type="aff" rid="af4">4</xref><xref ref-type="aff" rid="af5">5</xref><xref ref-type="corresp" rid="cor1">*</xref></contrib></contrib-group><aff id="af1"><label>1</label><addr-line>Department of Medicine, Division of Gerontology and Geriatric Medicine</addr-line>,</aff><aff id="af2"><label>2</label><addr-line>Department of Medicine, Division of Medical Genetics</addr-line>,</aff><aff id="af3"><label>3</label><addr-line>Department of Biostatistics</addr-line>,</aff><aff id="af4"><label>4</label><addr-line>Department of Neurology and Pharmacology</addr-line>, <institution>University of Washington</institution>, <addr-line>Seattle, WA 98195</addr-line>, <country>USA</country>,</aff><aff id="af5"><label>5</label><institution>Geriatric Research Education and Clinical Center</institution>, <addr-line>Veterans Affairs Puget Sound Health Care System, Seattle Division, Seattle, WA 98108</addr-line>, <country>USA</country>,</aff><aff id="af6"><label>6</label><addr-line>Department of Anthropology, Laboratory of Biomedical Anthropology and Neurosciences</addr-line>, <institution>Binghamton University</institution>, <addr-line>SUNY-Binghamton, NY 13902-6000</addr-line>, <country>USA</country>,</aff><aff id="af7"><label>7</label><addr-line>Department of Neuropathology</addr-line>, <institution>Tokyo Metropolitan Institute for Neuroscience</institution>, <addr-line>Tokyo</addr-line>, <country>Japan</country>,</aff><aff id="af8"><label>8</label><institution>University of Guam</institution>, <addr-line>Mangilao, Guam 96923</addr-line>, <country>USA</country> and</aff><aff id="af9"><label>9</label><addr-line>Department of Neurosciences</addr-line>, <institution>University of California</institution>, <addr-line>San Diego, La Jolla CA 92093-0662</addr-line>, <country>USA</country></aff><author-notes><corresp id="cor1"><label>*</label>To whom correspondence should be addressed at: <addr-line>GRECC S-182B, Veterans Affairs Puget Sound Health Care System, 1660 S. Columbian Way, Seattle, WA 98108</addr-line>, <country>USA</country>. Tel: <phone>+1 2067642701</phone>; Fax: <fax>+1 2067642569</fax>; Email: <email>zachdad@u.washington.edu</email></corresp></author-notes><pub-date pub-type="ppub"><day>1</day><month>February</month><year>2007</year></pub-date><pub-date pub-type="epub"><day>21</day><month>12</month><year>2006</year></pub-date><volume>16</volume><issue>3</issue><fpage>295</fpage><lpage>306</lpage><history><date date-type="received"><day>7</day><month>10</month><year>2006</year></date><date date-type="accepted"><day>6</day><month>12</month><year>2006</year></date></history><copyright-statement>Published by Oxford University Press 2006</copyright-statement><copyright-year>2007</copyright-year><abstract><p>Unusual forms of amyotrophic lateral sclerosis (ALS-G), Parkinsonism dementia complex (PDC-G) and Guam dementia (GD) are found in Chamorros, the indigenous people of Guam. Neurofibrillary tangles composed of hyperphosphorylated tau are a neuropathologic feature of these closely related disorders. To determine if variation in the gene that encodes microtubule-associated protein tau gene (<italic>MAPT</italic>) contributes to risk for these disorders, we genotyped nine single nucleotide polymorphism (SNP) sites and one insertion/deletion in the 5′ end of <italic>MAPT</italic> in 54 ALS-G, 135 PDC-G, 153 GD and 258 control subjects, all of whom are Chamorros. Variation at three SNPs (sites 2, 6 and 9) influenced risk for ALS-G, PDC-G and GD. SNP2 acts through a dominant mechanism and is independent of the risk conferred by SNPs 6 and 9, the latter two acting by a recessive mechanism. Persons with the high-risk SNP6 and SNP9 AC/AC diplotype had an increased risk of 3-fold [95% confidence interval (CI)=1.10–8.25] for GD, 4-fold (95% CI=1.40–11.64) for PDC-G and 6-fold (95% CI=1.44–32.14) for ALS-G, compared to persons with other diplotypes after adjusting for SNP2. Carriers of the SNP2 G allele had an increased risk of 1.6-fold (95% CI=1.00–2.62) for GD, 2-fold (95% CI=1.28–3.66) for PDC-G, and 1.5-fold (95% CI=0.74–3.00) for ALS-G, compared to non-carriers after adjusting for SNPs 6 and 9. Others have shown that SNP6 is also associated with risk for progressive supranuclear palsy. These two independent <italic>cis</italic>-acting sites presumably influence risk for Guam neuro-degenerative disorders by regulating <italic>MAPT</italic> expression.</p></abstract></article-meta></front></article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo><title>Two sites in the MAPT region confer genetic risk for Guam ALS/PDC and dementia</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>Two sites in the MAPT region confer genetic risk for Guam ALS/PDC and dementia</title></titleInfo><name type="personal"><namePart type="given">Purnima Desai</namePart><namePart type="family">Sundar</namePart><affiliation></affiliation><affiliation></affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Chang-En</namePart><namePart type="family">Yu</namePart><affiliation></affiliation><affiliation></affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Weiva</namePart><namePart type="family">Sieh</namePart><affiliation></affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Ellen</namePart><namePart type="family">Steinbart</namePart><affiliation></affiliation><affiliation></affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Ralph M.</namePart><namePart type="family">Garruto</namePart><affiliation>000, USA,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Kiyomitsu</namePart><namePart type="family">Oyanagi</namePart><affiliation></affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Ulla-Katrina</namePart><namePart type="family">Craig</namePart><affiliation></affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Thomas D.</namePart><namePart type="family">Bird</namePart><affiliation></affiliation><affiliation></affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Ellen M.</namePart><namePart type="family">Wijsman</namePart><affiliation></affiliation><affiliation></affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Douglas R.</namePart><namePart type="family">Galasko</namePart><affiliation>2093-0662, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal" displayLabel="corresp"><namePart type="given">Gerard D.</namePart><namePart type="family">Schellenberg</namePart><affiliation></affiliation><affiliation></affiliation><affiliation></affiliation><affiliation>E-mail: zachdad@u.washington.edu</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="research-article"></genre><subject><topic>ARTICLES</topic></subject><originInfo><publisher>Oxford University Press</publisher><dateIssued encoding="w3cdtf">2007-02-01</dateIssued><dateCreated encoding="w3cdtf">2006-12-21</dateCreated><copyrightDate encoding="w3cdtf">2007</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType></physicalDescription><abstract>Unusual forms of amyotrophic lateral sclerosis (ALS-G), Parkinsonism dementia complex (PDC-G) and Guam dementia (GD) are found in Chamorros, the indigenous people of Guam. Neurofibrillary tangles composed of hyperphosphorylated tau are a neuropathologic feature of these closely related disorders. To determine if variation in the gene that encodes microtubule-associated protein tau gene (MAPT) contributes to risk for these disorders, we genotyped nine single nucleotide polymorphism (SNP) sites and one insertion/deletion in the 5 end of MAPT in 54 ALS-G, 135 PDC-G, 153 GD and 258 control subjects, all of whom are Chamorros. Variation at three SNPs (sites 2, 6 and 9) influenced risk for ALS-G, PDC-G and GD. SNP2 acts through a dominant mechanism and is independent of the risk conferred by SNPs 6 and 9, the latter two acting by a recessive mechanism. Persons with the high-risk SNP6 and SNP9 AC/AC diplotype had an increased risk of 3-fold [95 confidence interval (CI)1.108.25] for GD, 4-fold (95 CI1.4011.64) for PDC-G and 6-fold (95 CI1.4432.14) for ALS-G, compared to persons with other diplotypes after adjusting for SNP2. Carriers of the SNP2 G allele had an increased risk of 1.6-fold (95 CI1.002.62) for GD, 2-fold (95 CI1.283.66) for PDC-G, and 1.5-fold (95 CI0.743.00) for ALS-G, compared to non-carriers after adjusting for SNPs 6 and 9. Others have shown that SNP6 is also associated with risk for progressive supranuclear palsy. These two independent cis-acting sites presumably influence risk for Guam neuro-degenerative disorders by regulating MAPT expression.</abstract><relatedItem type="host"><titleInfo><title>Human Molecular Genetics</title></titleInfo><genre type="Journal">journal</genre><identifier type="ISSN">0964-6906</identifier><identifier type="eISSN">1460-2083</identifier><identifier type="PublisherID">hmg</identifier><identifier type="PublisherID-hwp">hmg</identifier><part><date>2007</date><detail type="volume"><caption>vol.</caption><number>16</number></detail><detail type="issue"><caption>no.</caption><number>3</number></detail><extent unit="pages"><start>295</start><end>306</end></extent></part></relatedItem><identifier type="istex">2C3AD66B511CAEDC5F43F85522DAEA593774CDF3</identifier><identifier type="DOI">10.1093/hmg/ddl463</identifier><identifier type="ArticleID">ddl463</identifier><accessCondition type="use and reproduction" contentType="copyright">Published by Oxford University Press 2006</accessCondition><recordInfo><recordContentSource>OUP</recordContentSource></recordInfo></mods></metadata><covers><json:item><original>true</original><mimetype>image/tiff</mimetype><extension>tiff</extension><uri>https://api.istex.fr/document/2C3AD66B511CAEDC5F43F85522DAEA593774CDF3/covers/tiff</uri></json:item><json:item><original>true</original><mimetype>text/html</mimetype><extension>html</extension><uri>https://api.istex.fr/document/2C3AD66B511CAEDC5F43F85522DAEA593774CDF3/covers/html</uri></json:item></covers><annexes><json:item><original>true</original><mimetype>image/jpeg</mimetype><extension>jpeg</extension><uri>https://api.istex.fr/document/2C3AD66B511CAEDC5F43F85522DAEA593774CDF3/annexes/jpeg</uri></json:item><json:item><original>true</original><mimetype>image/gif</mimetype><extension>gif</extension><uri>https://api.istex.fr/document/2C3AD66B511CAEDC5F43F85522DAEA593774CDF3/annexes/gif</uri></json:item></annexes><enrichments><istex:catWosTEI uri="https://api.istex.fr/document/2C3AD66B511CAEDC5F43F85522DAEA593774CDF3/enrichments/catWos"><teiHeader><profileDesc><textClass><classCode scheme="WOS">BIOCHEMISTRY & MOLECULAR BIOLOGY</classCode><classCode scheme="WOS">GENETICS & HEREDITY</classCode></textClass></profileDesc></teiHeader></istex:catWosTEI></enrichments><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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