The sepiapterin reductase gene region reveals association in the PARK3 locus: analysis of familial and sporadic Parkinson’s disease in European populations
Identifieur interne : 001A21 ( Main/Corpus ); précédent : 001A20; suivant : 001A22The sepiapterin reductase gene region reveals association in the PARK3 locus: analysis of familial and sporadic Parkinson’s disease in European populations
Auteurs : M. Sharma ; J C Mueller ; A. Zimprich ; P. Lichtner ; A. Hofer ; P. Leitner ; S. Maass ; D. Berg ; A. Dürr ; V. Bonifati ; G. De Michele ; B. Oostra ; A. Brice ; N W Wood ; B. Muller-Myhsok ; T. GasserSource :
- Journal of Medical Genetics [ 0022-2593 ] ; 2006-07.
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- KwdEn :
Abstract
Background: Parkinson’s disease is a genetically complex disease with mixed mode of inheritance. Recently, a haplotype across the sepiapterin reductase (SPR) gene, which is located in the PARK3 linkage region, was shown to modulate age of onset of Parkinson’s disease in sibships from North America. Objective: To make a thorough assessment of the SPR gene region in sporadic Parkinson’s disease. Methods: A linkage study in 122 European sibship families with five microsatellite and 17 single nucleotide polymorphism (SNP) markers in and around the SPR gene region, and an association analysis in 340 sporadic cases of Parkinson’s disease and 680 control subjects from Germany with 40 SNPs. Linkage was evaluated by non-parametric linkage scores and genotypic or haplotype association was tested by regression analysis, assuming different risk effect models. Results: Significant LOD scores between 2 and 3 were obtained at the two SPR-flanking markers D2S2110 and D2S1394 and seven SNP markers around the SPR gene. We found the previously reported promoter SNP rs1876487 also significantly associated with age of onset in our sib pair families (p-value 0.02). One strong linkage disequilibrium (LD) block of 45 kb including the entire SPR gene was observed. Within this LD block all 14 inter-correlated SNPs were significantly associated with Parkinson’s disease affection status (p-value 0.004). Conclusions: DNA polymorphisms in a highly intercorrelated LD block, which includes the SPR gene, appear to be associated with both sporadic and familial Parkinson’s disease. This confirms a previous study showing that SPR potentially modulates the onset of or risk for Parkinson’s disease.
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DOI: 10.1136/jmg.2005.039149
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Sharma</name><affiliation><mods:affiliation>Hertie-Institute for Clinical Brain Research, Department of Neurodegenerative Diseases, University of Tübingen, Tübingen, Germany</mods:affiliation></affiliation></author><author><name sortKey="Mueller, J C" sort="Mueller, J C" uniqKey="Mueller J" first="J C" last="Mueller">J C Mueller</name><affiliation><mods:affiliation>Hertie-Institute for Clinical Brain Research, Department of Neurodegenerative Diseases, University of Tübingen, Tübingen, Germany</mods:affiliation></affiliation><affiliation><mods:affiliation>Institute for Medical Statistics and Epidemiology and Institute for Psychiatry and Psychotherapy, Technical University Munich, Munich, Germany</mods:affiliation></affiliation></author><author><name sortKey="Zimprich, A" sort="Zimprich, A" uniqKey="Zimprich A" first="A" last="Zimprich">A. Zimprich</name><affiliation><mods:affiliation>Department of Neurology, Medical University of Vienna, Vienna, Austria</mods:affiliation></affiliation></author><author><name sortKey="Lichtner, P" sort="Lichtner, P" uniqKey="Lichtner P" first="P" last="Lichtner">P. Lichtner</name><affiliation><mods:affiliation>Institute for Human Genetics–National Research Centre for Environment and Health, Neuherberg, Germany</mods:affiliation></affiliation></author><author><name sortKey="Hofer, A" sort="Hofer, A" uniqKey="Hofer A" first="A" last="Hofer">A. Hofer</name><affiliation><mods:affiliation>Hertie-Institute for Clinical Brain Research, Department of Neurodegenerative Diseases, University of Tübingen, Tübingen, Germany</mods:affiliation></affiliation></author><author><name sortKey="Leitner, P" sort="Leitner, P" uniqKey="Leitner P" first="P" last="Leitner">P. Leitner</name><affiliation><mods:affiliation>Hertie-Institute for Clinical Brain Research, Department of Neurodegenerative Diseases, University of Tübingen, Tübingen, Germany</mods:affiliation></affiliation></author><author><name sortKey="Maass, S" sort="Maass, S" uniqKey="Maass S" first="S" last="Maass">S. Maass</name><affiliation><mods:affiliation>Department of Neurology, Ludwig-Maximilians-University, Munich, Germany</mods:affiliation></affiliation></author><author><name sortKey="Berg, D" sort="Berg, D" uniqKey="Berg D" first="D" last="Berg">D. Berg</name><affiliation><mods:affiliation>Department for Medical Genetics, Eberhard Karls University Tübingen, Tübingen, Germany</mods:affiliation></affiliation></author><author><name sortKey="Durr, A" sort="Durr, A" uniqKey="Durr A" first="A" last="Dürr">A. Dürr</name><affiliation><mods:affiliation>INSERM U289 and Department of Genetics, Cytogenetics and Embryology, AP-HP, Salpetriere Hospital, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Bonifati, V" sort="Bonifati, V" uniqKey="Bonifati V" first="V" last="Bonifati">V. Bonifati</name><affiliation><mods:affiliation>Department of Neurological Sciences, University La Sapienza, Rome, Italy</mods:affiliation></affiliation></author><author><name sortKey="De Michele, G" sort="De Michele, G" uniqKey="De Michele G" first="G" last="De Michele">G. De Michele</name><affiliation><mods:affiliation>Department of Clinical Genetics, Erasmus University, Rotterdam, Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Oostra, B" sort="Oostra, B" uniqKey="Oostra B" first="B" last="Oostra">B. Oostra</name><affiliation><mods:affiliation>Department of Neurological Sciences, Federico II University, Naples, Italy</mods:affiliation></affiliation></author><author><name sortKey="Brice, A" sort="Brice, A" uniqKey="Brice A" first="A" last="Brice">A. Brice</name><affiliation><mods:affiliation>INSERM U289 and Department of Genetics, Cytogenetics and Embryology, AP-HP, Salpetriere Hospital, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Wood, N W" sort="Wood, N W" uniqKey="Wood N" first="N W" last="Wood">N W Wood</name><affiliation><mods:affiliation>Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK</mods:affiliation></affiliation></author><author><name sortKey="Muller Myhsok, B" sort="Muller Myhsok, B" uniqKey="Muller Myhsok B" first="B" last="Muller-Myhsok">B. Muller-Myhsok</name><affiliation><mods:affiliation>Max-Planck Institute for Psychiatry, Munich, Germany</mods:affiliation></affiliation></author><author><name sortKey="Gasser, T" sort="Gasser, T" uniqKey="Gasser T" first="T" last="Gasser">T. Gasser</name><affiliation><mods:affiliation>Hertie-Institute for Clinical Brain Research, Department of Neurodegenerative Diseases, University of Tübingen, Tübingen, Germany</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Journal of Medical Genetics</title><title level="j" type="abbrev">J Med Genet</title><idno type="ISSN">0022-2593</idno><idno type="eISSN">1468-6244</idno><imprint><publisher>BMJ Publishing Group Ltd</publisher><date type="published" when="2006-07">2006-07</date><biblScope unit="volume">43</biblScope><biblScope unit="issue">7</biblScope><biblScope unit="page" from="557">557</biblScope></imprint><idno type="ISSN">0022-2593</idno></series><idno type="istex">EAE8C17042AF64FE4310E7317F422141F45B6A58</idno><idno type="DOI">10.1136/jmg.2005.039149</idno><idno type="href">jmedgenet-43-557.pdf</idno><idno type="PMID">16443856</idno><idno type="PII">1468-6422</idno><idno type="local">0430557</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0022-2593</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>LD, linkage disequilibrium</term><term>MAF, minor allele frequency</term><term>NPL, non-parametric linkage scores</term><term>PARK3</term><term>Parkinson’s disease</term><term>SNP, single nucleotide polymorphism</term><term>SPR, sepiapterin reductase</term><term>STR, short tandem repeat</term><term>linkage disequilibrium</term><term>sepiapterin reductase</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Background: Parkinson’s disease is a genetically complex disease with mixed mode of inheritance. Recently, a haplotype across the sepiapterin reductase (SPR) gene, which is located in the PARK3 linkage region, was shown to modulate age of onset of Parkinson’s disease in sibships from North America. Objective: To make a thorough assessment of the SPR gene region in sporadic Parkinson’s disease. Methods: A linkage study in 122 European sibship families with five microsatellite and 17 single nucleotide polymorphism (SNP) markers in and around the SPR gene region, and an association analysis in 340 sporadic cases of Parkinson’s disease and 680 control subjects from Germany with 40 SNPs. Linkage was evaluated by non-parametric linkage scores and genotypic or haplotype association was tested by regression analysis, assuming different risk effect models. Results: Significant LOD scores between 2 and 3 were obtained at the two SPR-flanking markers D2S2110 and D2S1394 and seven SNP markers around the SPR gene. We found the previously reported promoter SNP rs1876487 also significantly associated with age of onset in our sib pair families (p-value 0.02). One strong linkage disequilibrium (LD) block of 45 kb including the entire SPR gene was observed. Within this LD block all 14 inter-correlated SNPs were significantly associated with Parkinson’s disease affection status (p-value 0.004). Conclusions: DNA polymorphisms in a highly intercorrelated LD block, which includes the SPR gene, appear to be associated with both sporadic and familial Parkinson’s disease. This confirms a previous study showing that SPR potentially modulates the onset of or risk for Parkinson’s disease.</div></front></TEI><istex><corpusName>bmj</corpusName><author><json:item><name>M Sharma</name><affiliations><json:string>Hertie-Institute for Clinical Brain Research, Department of Neurodegenerative Diseases, University of Tübingen, Tübingen, Germany</json:string></affiliations></json:item><json:item><name>J C Mueller</name><affiliations><json:string>Hertie-Institute for Clinical Brain Research, Department of Neurodegenerative Diseases, University of Tübingen, Tübingen, Germany</json:string><json:string>Institute for Medical Statistics and Epidemiology and Institute for Psychiatry and Psychotherapy, Technical University Munich, Munich, Germany</json:string></affiliations></json:item><json:item><name>A Zimprich</name><affiliations><json:string>Department of Neurology, Medical University of Vienna, Vienna, Austria</json:string></affiliations></json:item><json:item><name>P Lichtner</name><affiliations><json:string>Institute for Human Genetics–National Research Centre for Environment and Health, Neuherberg, Germany</json:string></affiliations></json:item><json:item><name>A Hofer</name><affiliations><json:string>Hertie-Institute for Clinical Brain Research, Department of Neurodegenerative Diseases, University of Tübingen, Tübingen, Germany</json:string></affiliations></json:item><json:item><name>P Leitner</name><affiliations><json:string>Hertie-Institute for Clinical Brain Research, Department of Neurodegenerative Diseases, University of Tübingen, Tübingen, Germany</json:string></affiliations></json:item><json:item><name>S Maass</name><affiliations><json:string>Department of Neurology, Ludwig-Maximilians-University, Munich, Germany</json:string></affiliations></json:item><json:item><name>D Berg</name><affiliations><json:string>Department for Medical Genetics, Eberhard Karls University Tübingen, Tübingen, Germany</json:string></affiliations></json:item><json:item><name>A Dürr</name><affiliations><json:string>INSERM U289 and Department of Genetics, Cytogenetics and Embryology, AP-HP, Salpetriere Hospital, Paris, France</json:string></affiliations></json:item><json:item><name>V Bonifati</name><affiliations><json:string>Department of Neurological Sciences, University La Sapienza, Rome, Italy</json:string></affiliations></json:item><json:item><name>G De Michele</name><affiliations><json:string>Department of Clinical Genetics, Erasmus University, Rotterdam, Netherlands</json:string></affiliations></json:item><json:item><name>B Oostra</name><affiliations><json:string>Department of Neurological Sciences, Federico II University, Naples, Italy</json:string></affiliations></json:item><json:item><name>A Brice</name><affiliations><json:string>INSERM U289 and Department of Genetics, Cytogenetics and Embryology, AP-HP, Salpetriere Hospital, Paris, France</json:string></affiliations></json:item><json:item><name>N W Wood</name><affiliations><json:string>Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK</json:string></affiliations></json:item><json:item><name>B Muller-Myhsok</name><affiliations><json:string>Max-Planck Institute for Psychiatry, Munich, Germany</json:string></affiliations></json:item><json:item><name>T Gasser</name><affiliations><json:string>Hertie-Institute for Clinical Brain Research, Department of Neurodegenerative Diseases, University of Tübingen, Tübingen, Germany</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Original articles</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Clinical genetics</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Genetic screening / counselling</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>LD, linkage disequilibrium</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>MAF, minor allele frequency</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>NPL, non-parametric linkage scores</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>SNP, single nucleotide polymorphism</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>SPR, sepiapterin reductase</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>STR, short tandem repeat</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>linkage disequilibrium</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>PARK3</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Parkinson’s disease</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>sepiapterin reductase</value></json:item></subject><language><json:string>eng</json:string></language><abstract>Background: Parkinson’s disease is a genetically complex disease with mixed mode of inheritance. Recently, a haplotype across the sepiapterin reductase (SPR) gene, which is located in the PARK3 linkage region, was shown to modulate age of onset of Parkinson’s disease in sibships from North America. Objective: To make a thorough assessment of the SPR gene region in sporadic Parkinson’s disease. Methods: A linkage study in 122 European sibship families with five microsatellite and 17 single nucleotide polymorphism (SNP) markers in and around the SPR gene region, and an association analysis in 340 sporadic cases of Parkinson’s disease and 680 control subjects from Germany with 40 SNPs. Linkage was evaluated by non-parametric linkage scores and genotypic or haplotype association was tested by regression analysis, assuming different risk effect models. Results: Significant LOD scores between 2 and 3 were obtained at the two SPR-flanking markers D2S2110 and D2S1394 and seven SNP markers around the SPR gene. We found the previously reported promoter SNP rs1876487 also significantly associated with age of onset in our sib pair families (p-value 0.02). One strong linkage disequilibrium (LD) block of 45 kb including the entire SPR gene was observed. Within this LD block all 14 inter-correlated SNPs were significantly associated with Parkinson’s disease affection status (p-value 0.004). Conclusions: DNA polymorphisms in a highly intercorrelated LD block, which includes the SPR gene, appear to be associated with both sporadic and familial Parkinson’s disease. This confirms a previous study showing that SPR potentially modulates the onset of or risk for Parkinson’s disease.</abstract><qualityIndicators><score>6.915</score><pdfVersion>1.2</pdfVersion><pdfPageSize>612 x 792 pts (letter)</pdfPageSize><refBibsNative>false</refBibsNative><keywordCount>13</keywordCount><abstractCharCount>1689</abstractCharCount><pdfWordCount>3915</pdfWordCount><pdfCharCount>28621</pdfCharCount><pdfPageCount>6</pdfPageCount><abstractWordCount>253</abstractWordCount></qualityIndicators><title>The sepiapterin reductase gene region reveals association in the PARK3 locus: analysis of familial and sporadic Parkinson’s disease in European populations</title><pmid><json:string>16443856</json:string></pmid><genre><json:string>research-article</json:string></genre><host><volume>43</volume><pages><first>557</first></pages><issn><json:string>0022-2593</json:string></issn><issue>7</issue><genre></genre><language><json:string>unknown</json:string></language><eissn><json:string>1468-6244</json:string></eissn><title>Journal of Medical Genetics</title></host><publicationDate>2006</publicationDate><copyrightDate>2006</copyrightDate><doi><json:string>10.1136/jmg.2005.039149</json:string></doi><id>EAE8C17042AF64FE4310E7317F422141F45B6A58</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/EAE8C17042AF64FE4310E7317F422141F45B6A58/fulltext/pdf</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/EAE8C17042AF64FE4310E7317F422141F45B6A58/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/EAE8C17042AF64FE4310E7317F422141F45B6A58/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">The sepiapterin reductase gene region reveals association in the PARK3 locus: analysis of familial and sporadic Parkinson’s disease in European populations</title><respStmt xml:id="ISTEX-API" resp="Références bibliographiques récupérées via GROBID" name="ISTEX-API (INIST-CNRS)"></respStmt></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>BMJ Publishing Group Ltd</publisher><availability><p>BMJ</p></availability><date>2006-01-27</date></publicationStmt><notesStmt><note>Correspondence to:
Prof Dr med Thomas Gasser
Hertie-Institute for Clinical Brain Research, Department for Neurodegenerative Diseases, University of Tübingen, Hoppe-Seyler Str 3, 72076 Tübingen, Germany; Thomas.Gasser@med.uni-tuebingen.de</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">The sepiapterin reductase gene region reveals association in the PARK3 locus: analysis of familial and sporadic Parkinson’s disease in European populations</title><author><persName><forename type="first">M</forename><surname>Sharma</surname></persName><affiliation>Hertie-Institute for Clinical Brain Research, Department of Neurodegenerative Diseases, University of Tübingen, Tübingen, Germany</affiliation></author><author><persName><forename type="first">J C</forename><surname>Mueller</surname></persName><affiliation>Hertie-Institute for Clinical Brain Research, Department of Neurodegenerative Diseases, University of Tübingen, Tübingen, Germany</affiliation><affiliation>Institute for Medical Statistics and Epidemiology and Institute for Psychiatry and Psychotherapy, Technical University Munich, Munich, Germany</affiliation></author><author><persName><forename type="first">A</forename><surname>Zimprich</surname></persName><affiliation>Department of Neurology, Medical University of Vienna, Vienna, Austria</affiliation></author><author><persName><forename type="first">P</forename><surname>Lichtner</surname></persName><affiliation>Institute for Human Genetics–National Research Centre for Environment and Health, Neuherberg, Germany</affiliation></author><author><persName><forename type="first">A</forename><surname>Hofer</surname></persName><affiliation>Hertie-Institute for Clinical Brain Research, Department of Neurodegenerative Diseases, University of Tübingen, Tübingen, Germany</affiliation></author><author><persName><forename type="first">P</forename><surname>Leitner</surname></persName><affiliation>Hertie-Institute for Clinical Brain Research, Department of Neurodegenerative Diseases, University of Tübingen, Tübingen, Germany</affiliation></author><author><persName><forename type="first">S</forename><surname>Maass</surname></persName><affiliation>Department of Neurology, Ludwig-Maximilians-University, Munich, Germany</affiliation></author><author><persName><forename type="first">D</forename><surname>Berg</surname></persName><affiliation>Department for Medical Genetics, Eberhard Karls University Tübingen, Tübingen, Germany</affiliation></author><author><persName><forename type="first">A</forename><surname>Dürr</surname></persName><affiliation>INSERM U289 and Department of Genetics, Cytogenetics and Embryology, AP-HP, Salpetriere Hospital, Paris, France</affiliation></author><author><persName><forename type="first">V</forename><surname>Bonifati</surname></persName><affiliation>Department of Neurological Sciences, University La Sapienza, Rome, Italy</affiliation></author><author><persName><forename type="first">G</forename><surname>De Michele</surname></persName><affiliation>Department of Clinical Genetics, Erasmus University, Rotterdam, Netherlands</affiliation></author><author><persName><forename type="first">B</forename><surname>Oostra</surname></persName><affiliation>Department of Neurological Sciences, Federico II University, Naples, Italy</affiliation></author><author><persName><forename type="first">A</forename><surname>Brice</surname></persName><affiliation>INSERM U289 and Department of Genetics, Cytogenetics and Embryology, AP-HP, Salpetriere Hospital, Paris, France</affiliation></author><author><persName><forename type="first">N W</forename><surname>Wood</surname></persName><affiliation>Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK</affiliation></author><author><persName><forename type="first">B</forename><surname>Muller-Myhsok</surname></persName><affiliation>Max-Planck Institute for Psychiatry, Munich, Germany</affiliation></author><author><persName><forename type="first">T</forename><surname>Gasser</surname></persName><affiliation>Hertie-Institute for Clinical Brain Research, Department of Neurodegenerative Diseases, University of Tübingen, Tübingen, Germany</affiliation></author></analytic><monogr><title level="j">Journal of Medical Genetics</title><title level="j" type="abbrev">J Med Genet</title><idno type="pISSN">0022-2593</idno><idno type="eISSN">1468-6244</idno><imprint><publisher>BMJ Publishing Group Ltd</publisher><date type="published" when="2006-07"></date><biblScope unit="volume">43</biblScope><biblScope unit="issue">7</biblScope><biblScope unit="page" from="557">557</biblScope></imprint></monogr><idno type="istex">EAE8C17042AF64FE4310E7317F422141F45B6A58</idno><idno type="DOI">10.1136/jmg.2005.039149</idno><idno type="href">jmedgenet-43-557.pdf</idno><idno type="PMID">16443856</idno><idno type="PII">1468-6422</idno><idno type="local">0430557</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2006-01-27</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Background: Parkinson’s disease is a genetically complex disease with mixed mode of inheritance. Recently, a haplotype across the sepiapterin reductase (SPR) gene, which is located in the PARK3 linkage region, was shown to modulate age of onset of Parkinson’s disease in sibships from North America. Objective: To make a thorough assessment of the SPR gene region in sporadic Parkinson’s disease. Methods: A linkage study in 122 European sibship families with five microsatellite and 17 single nucleotide polymorphism (SNP) markers in and around the SPR gene region, and an association analysis in 340 sporadic cases of Parkinson’s disease and 680 control subjects from Germany with 40 SNPs. Linkage was evaluated by non-parametric linkage scores and genotypic or haplotype association was tested by regression analysis, assuming different risk effect models. Results: Significant LOD scores between 2 and 3 were obtained at the two SPR-flanking markers D2S2110 and D2S1394 and seven SNP markers around the SPR gene. We found the previously reported promoter SNP rs1876487 also significantly associated with age of onset in our sib pair families (p-value 0.02). One strong linkage disequilibrium (LD) block of 45 kb including the entire SPR gene was observed. Within this LD block all 14 inter-correlated SNPs were significantly associated with Parkinson’s disease affection status (p-value 0.004). Conclusions: DNA polymorphisms in a highly intercorrelated LD block, which includes the SPR gene, appear to be associated with both sporadic and familial Parkinson’s disease. This confirms a previous study showing that SPR potentially modulates the onset of or risk for Parkinson’s disease.</p></abstract><textClass><keywords scheme="keyword"><list><head>hwp-journal-coll</head><item><term>Clinical genetics</term></item></list></keywords></textClass><textClass><keywords scheme="keyword"><list><head>hwp-journal-coll</head><item><term>Genetic screening / counselling</term></item></list></keywords></textClass><textClass xml:lang="en"><keywords scheme="keyword"><list><head>ABR</head><item><term>LD, linkage disequilibrium</term></item><item><term>MAF, minor allele frequency</term></item><item><term>NPL, non-parametric linkage scores</term></item><item><term>SNP, single nucleotide polymorphism</term></item><item><term>SPR, sepiapterin reductase</term></item><item><term>STR, short tandem repeat</term></item></list></keywords></textClass><textClass xml:lang="en"><keywords scheme="keyword"><list><head>KWD</head><item><term>linkage disequilibrium</term></item><item><term>PARK3</term></item><item><term>Parkinson’s disease</term></item><item><term>sepiapterin reductase</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2006-01-27">Created</change><change when="2006-07">Published</change><change xml:id="refBibs-istex" who="#ISTEX-API" when="2016-3-14">References added</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/EAE8C17042AF64FE4310E7317F422141F45B6A58/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="corpus bmj" wicri:toSee="no header"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="no"</istex:xmlDeclaration><istex:docType PUBLIC="-//NLM//DTD Journal Archiving and Interchange DTD v2.3 20070202//EN" URI="archivearticle.dtd" name="istex:docType"></istex:docType><istex:document><article xml:lang="en" article-type="research-article"><front><journal-meta><journal-id journal-id-type="hwp">jmedgenet</journal-id><journal-id journal-id-type="nlm-ta">J Med Genet</journal-id><journal-title>Journal of Medical Genetics</journal-title><abbrev-journal-title abbrev-type="publisher">J Med Genet</abbrev-journal-title><issn pub-type="ppub">0022-2593</issn><issn pub-type="epub">1468-6244</issn><publisher><publisher-name>BMJ Publishing Group Ltd</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="other">0430557</article-id><article-id pub-id-type="doi">10.1136/jmg.2005.039149</article-id><article-id pub-id-type="pii">1468-6422</article-id><article-id pub-id-type="other">jmedgenet;43/7/557</article-id><article-id pub-id-type="other">jmedgenet;jmg.2005.039149</article-id><article-id pub-id-type="pmid">16443856</article-id><article-id pub-id-type="other">557</article-id><article-id pub-id-type="other">jmg.2005.039149</article-id><article-categories><subj-group subj-group-type="heading"><subject content-type="original">Original articles</subject></subj-group><subj-group subj-group-type="hwp-journal-coll"><subject>Clinical genetics</subject></subj-group><subj-group subj-group-type="hwp-journal-coll"><subject>Genetic screening / counselling</subject></subj-group></article-categories><title-group><article-title>The sepiapterin reductase gene region reveals association in the <italic>PARK3</italic> locus: analysis of familial and sporadic Parkinson’s disease in European populations</article-title></title-group><contrib-group><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Sharma</surname><given-names>M</given-names></name><xref rid="AFF1">1</xref><xref rid="FN1">*</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Mueller</surname><given-names>J C</given-names></name><xref rid="AFF1">1</xref><xref rid="AFF2">2</xref><xref rid="FN1">*</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Zimprich</surname><given-names>A</given-names></name><xref rid="AFF3">3</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Lichtner</surname><given-names>P</given-names></name><xref rid="AFF4">4</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Hofer</surname><given-names>A</given-names></name><xref rid="AFF1">1</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Leitner</surname><given-names>P</given-names></name><xref rid="AFF1">1</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Maass</surname><given-names>S</given-names></name><xref rid="AFF5">5</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Berg</surname><given-names>D</given-names></name><xref rid="AFF6">6</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Dürr</surname><given-names>A</given-names></name><xref rid="AFF7">7</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Bonifati</surname><given-names>V</given-names></name><xref rid="AFF8">8</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>De Michele</surname><given-names>G</given-names></name><xref rid="AFF9">9</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Oostra</surname><given-names>B</given-names></name><xref rid="AFF10">10</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Brice</surname><given-names>A</given-names></name><xref rid="AFF7">7</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Wood</surname><given-names>N W</given-names></name><xref rid="AFF11">11</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Muller-Myhsok</surname><given-names>B</given-names></name><xref rid="AFF12">12</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Gasser</surname><given-names>T</given-names></name><xref rid="AFF1">1</xref></contrib><contrib contrib-type="group-author" xlink:type="simple"><on-behalf-of>European Consortium on Genetic Susceptibility in Parkinson’s Disease (GSPD)</on-behalf-of></contrib><aff id="AFF1"><label>1</label>Hertie-Institute for Clinical Brain Research, Department of Neurodegenerative Diseases, University of Tübingen, Tübingen, Germany</aff><aff id="AFF2"><label>2</label>Institute for Medical Statistics and Epidemiology and Institute for Psychiatry and Psychotherapy, Technical University Munich, Munich, Germany</aff><aff id="AFF3"><label>3</label>Department of Neurology, Medical University of Vienna, Vienna, Austria</aff><aff id="AFF4"><label>4</label>Institute for Human Genetics–National Research Centre for Environment and Health, Neuherberg, Germany</aff><aff id="AFF5"><label>5</label>Department of Neurology, Ludwig-Maximilians-University, Munich, Germany</aff><aff id="AFF6"><label>6</label>Department for Medical Genetics, Eberhard Karls University Tübingen, Tübingen, Germany</aff><aff id="AFF7"><label>7</label>INSERM U289 and Department of Genetics, Cytogenetics and Embryology, AP-HP, Salpetriere Hospital, Paris, France</aff><aff id="AFF8"><label>8</label>Department of Neurological Sciences, University La Sapienza, Rome, Italy</aff><aff id="AFF9"><label>9</label>Department of Clinical Genetics, Erasmus University, Rotterdam, Netherlands</aff><aff id="AFF10"><label>10</label>Department of Neurological Sciences, Federico II University, Naples, Italy</aff><aff id="AFF11"><label>11</label>Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK</aff><aff id="AFF12"><label>12</label>Max-Planck Institute for Psychiatry, Munich, Germany</aff></contrib-group><author-notes><corresp>Correspondence to:
Prof Dr med Thomas Gasser
Hertie-Institute for Clinical Brain Research, Department for Neurodegenerative Diseases, University of Tübingen, Hoppe-Seyler Str 3, 72076 Tübingen, Germany; <ext-link xlink:href="Thomas.Gasser@med.uni-tuebingen.de" ext-link-type="email" xlink:type="simple">Thomas.Gasser@med.uni-tuebingen.de</ext-link></corresp></author-notes><pub-date pub-type="ppub"><month>7</month><year>2006</year></pub-date><pub-date pub-type="epub"><day>27</day><month>1</month><year>2006</year></pub-date><volume>43</volume><volume-id pub-id-type="other">43</volume-id><volume-id pub-id-type="other">43</volume-id><issue>7</issue><issue-id pub-id-type="other">jmedgenet;43/7</issue-id><issue-id pub-id-type="other">7</issue-id><issue-id pub-id-type="other">43/7</issue-id><fpage>557</fpage><history><date date-type="accepted"><day>05</day><month>01</month><year>2006</year></date><date date-type="received"><day>25</day><month>10</month><year>2005</year></date><date date-type="rev-recd"><day>04</day><month>01</month><year>2006</year></date></history><permissions><copyright-statement>Copyright 2006 Journal of Medical Genetics</copyright-statement><copyright-year>2006</copyright-year></permissions><self-uri content-type="pdf" xlink:role="full-text" xlink:href="jmedgenet-43-557.pdf"></self-uri><abstract xml:lang="en"><p><bold>Background:</bold> Parkinson’s disease is a genetically complex disease with mixed mode of inheritance. Recently, a haplotype across the sepiapterin reductase (SPR) gene, which is located in the PARK3 linkage region, was shown to modulate age of onset of Parkinson’s disease in sibships from North America.</p><p><bold>Objective:</bold> To make a thorough assessment of the SPR gene region in sporadic Parkinson’s disease.</p><p><bold>Methods:</bold> A linkage study in 122 European sibship families with five microsatellite and 17 single nucleotide polymorphism (SNP) markers in and around the SPR gene region, and an association analysis in 340 sporadic cases of Parkinson’s disease and 680 control subjects from Germany with 40 SNPs. Linkage was evaluated by non-parametric linkage scores and genotypic or haplotype association was tested by regression analysis, assuming different risk effect models.</p><p><bold>Results:</bold> Significant LOD scores between 2 and 3 were obtained at the two SPR-flanking markers D2S2110 and D2S1394 and seven SNP markers around the SPR gene. We found the previously reported promoter SNP rs1876487 also significantly associated with age of onset in our sib pair families (p-value 0.02). One strong linkage disequilibrium (LD) block of 45 kb including the entire SPR gene was observed. Within this LD block all 14 inter-correlated SNPs were significantly associated with Parkinson’s disease affection status (p-value 0.004).</p><p><bold>Conclusions:</bold> DNA polymorphisms in a highly intercorrelated LD block, which includes the SPR gene, appear to be associated with both sporadic and familial Parkinson’s disease. This confirms a previous study showing that SPR potentially modulates the onset of or risk for Parkinson’s disease.</p></abstract><kwd-group kwd-group-type="ABR" xml:lang="en"><kwd>LD, linkage disequilibrium</kwd><kwd>MAF, minor allele frequency</kwd><kwd>NPL, non-parametric linkage scores</kwd><kwd>SNP, single nucleotide polymorphism</kwd><kwd>SPR, sepiapterin reductase</kwd><kwd>STR, short tandem repeat</kwd></kwd-group><kwd-group kwd-group-type="KWD" xml:lang="en"><kwd>linkage disequilibrium</kwd><kwd>PARK3</kwd><kwd>Parkinson’s disease</kwd><kwd>sepiapterin reductase</kwd></kwd-group></article-meta></front></article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>The sepiapterin reductase gene region reveals association in the PARK3 locus: analysis of familial and sporadic Parkinson’s disease in European populations</title></titleInfo><titleInfo type="alternative" lang="en" contentType="CDATA"><title>The sepiapterin reductase gene region reveals association in the PARK3 locus: analysis of familial and sporadic Parkinson’s disease in European populations</title></titleInfo><name type="personal"><namePart type="given">M</namePart><namePart type="family">Sharma</namePart><affiliation>Hertie-Institute for Clinical Brain Research, Department of Neurodegenerative Diseases, University of Tübingen, Tübingen, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">J C</namePart><namePart type="family">Mueller</namePart><affiliation>Hertie-Institute for Clinical Brain Research, Department of Neurodegenerative Diseases, University of Tübingen, Tübingen, Germany</affiliation><affiliation>Institute for Medical Statistics and Epidemiology and Institute for Psychiatry and Psychotherapy, Technical University Munich, Munich, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">A</namePart><namePart type="family">Zimprich</namePart><affiliation>Department of Neurology, Medical University of Vienna, Vienna, Austria</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">P</namePart><namePart type="family">Lichtner</namePart><affiliation>Institute for Human Genetics–National Research Centre for Environment and Health, Neuherberg, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">A</namePart><namePart type="family">Hofer</namePart><affiliation>Hertie-Institute for Clinical Brain Research, Department of Neurodegenerative Diseases, University of Tübingen, Tübingen, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">P</namePart><namePart type="family">Leitner</namePart><affiliation>Hertie-Institute for Clinical Brain Research, Department of Neurodegenerative Diseases, University of Tübingen, Tübingen, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">S</namePart><namePart type="family">Maass</namePart><affiliation>Department of Neurology, Ludwig-Maximilians-University, Munich, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">D</namePart><namePart type="family">Berg</namePart><affiliation>Department for Medical Genetics, Eberhard Karls University Tübingen, Tübingen, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">A</namePart><namePart type="family">Dürr</namePart><affiliation>INSERM U289 and Department of Genetics, Cytogenetics and Embryology, AP-HP, Salpetriere Hospital, Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">V</namePart><namePart type="family">Bonifati</namePart><affiliation>Department of Neurological Sciences, University La Sapienza, Rome, Italy</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">G</namePart><namePart type="family">De Michele</namePart><affiliation>Department of Clinical Genetics, Erasmus University, Rotterdam, Netherlands</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">B</namePart><namePart type="family">Oostra</namePart><affiliation>Department of Neurological Sciences, Federico II University, Naples, Italy</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">A</namePart><namePart type="family">Brice</namePart><affiliation>INSERM U289 and Department of Genetics, Cytogenetics and Embryology, AP-HP, Salpetriere Hospital, Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">N W</namePart><namePart type="family">Wood</namePart><affiliation>Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">B</namePart><namePart type="family">Muller-Myhsok</namePart><affiliation>Max-Planck Institute for Psychiatry, Munich, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">T</namePart><namePart type="family">Gasser</namePart><affiliation>Hertie-Institute for Clinical Brain Research, Department of Neurodegenerative Diseases, University of Tübingen, Tübingen, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="research-article"></genre><subject><genre>hwp-journal-coll</genre><topic>Clinical genetics</topic></subject><subject><genre>hwp-journal-coll</genre><topic>Genetic screening / counselling</topic></subject><originInfo><publisher>BMJ Publishing Group Ltd</publisher><dateIssued encoding="w3cdtf">2006-07</dateIssued><dateCreated encoding="w3cdtf">2006-01-27</dateCreated><copyrightDate encoding="w3cdtf">2006</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 lang="en">Background: Parkinson’s disease is a genetically complex disease with mixed mode of inheritance. Recently, a haplotype across the sepiapterin reductase (SPR) gene, which is located in the PARK3 linkage region, was shown to modulate age of onset of Parkinson’s disease in sibships from North America. Objective: To make a thorough assessment of the SPR gene region in sporadic Parkinson’s disease. Methods: A linkage study in 122 European sibship families with five microsatellite and 17 single nucleotide polymorphism (SNP) markers in and around the SPR gene region, and an association analysis in 340 sporadic cases of Parkinson’s disease and 680 control subjects from Germany with 40 SNPs. Linkage was evaluated by non-parametric linkage scores and genotypic or haplotype association was tested by regression analysis, assuming different risk effect models. Results: Significant LOD scores between 2 and 3 were obtained at the two SPR-flanking markers D2S2110 and D2S1394 and seven SNP markers around the SPR gene. We found the previously reported promoter SNP rs1876487 also significantly associated with age of onset in our sib pair families (p-value 0.02). One strong linkage disequilibrium (LD) block of 45 kb including the entire SPR gene was observed. Within this LD block all 14 inter-correlated SNPs were significantly associated with Parkinson’s disease affection status (p-value 0.004). Conclusions: DNA polymorphisms in a highly intercorrelated LD block, which includes the SPR gene, appear to be associated with both sporadic and familial Parkinson’s disease. This confirms a previous study showing that SPR potentially modulates the onset of or risk for Parkinson’s disease.</abstract><note type="author-notes">Correspondence to:
Prof Dr med Thomas Gasser
Hertie-Institute for Clinical Brain Research, Department for Neurodegenerative Diseases, University of Tübingen, Hoppe-Seyler Str 3, 72076 Tübingen, Germany; Thomas.Gasser@med.uni-tuebingen.de</note><subject lang="en"><genre>ABR</genre><topic>LD, linkage disequilibrium</topic><topic>MAF, minor allele frequency</topic><topic>NPL, non-parametric linkage scores</topic><topic>SNP, single nucleotide polymorphism</topic><topic>SPR, sepiapterin reductase</topic><topic>STR, short tandem repeat</topic></subject><subject lang="en"><genre>KWD</genre><topic>linkage disequilibrium</topic><topic>PARK3</topic><topic>Parkinson’s disease</topic><topic>sepiapterin reductase</topic></subject><relatedItem type="host"><titleInfo><title>Journal of Medical Genetics</title></titleInfo><titleInfo type="abbreviated"><title>J Med Genet</title></titleInfo><genre type="Journal">journal</genre><identifier type="ISSN">0022-2593</identifier><identifier type="eISSN">1468-6244</identifier><identifier type="PublisherID-hwp">jmedgenet</identifier><identifier type="PublisherID-nlm-ta">J Med Genet</identifier><part><date>2006</date><detail type="volume"><caption>vol.</caption><number>43</number></detail><detail type="issue"><caption>no.</caption><number>7</number></detail><extent unit="pages"><start>557</start></extent></part></relatedItem><identifier type="istex">EAE8C17042AF64FE4310E7317F422141F45B6A58</identifier><identifier type="DOI">10.1136/jmg.2005.039149</identifier><identifier type="href">jmedgenet-43-557.pdf</identifier><identifier type="PMID">16443856</identifier><identifier type="PII">1468-6422</identifier><identifier type="local">0430557</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright 2006 Journal of Medical Genetics</accessCondition><recordInfo><recordContentSource>BMJ</recordContentSource></recordInfo></mods></metadata><annexes><json:item><original>true</original><mimetype>image/jpeg</mimetype><extension>jpeg</extension><uri>https://api.istex.fr/document/EAE8C17042AF64FE4310E7317F422141F45B6A58/annexes/jpeg</uri></json:item></annexes><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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