Peptidoglycan Recognition Protein Genes and Risk of Parkinson’s Disease
Identifieur interne : 000840 ( Pmc/Corpus ); précédent : 000839; suivant : 000841Peptidoglycan Recognition Protein Genes and Risk of Parkinson’s Disease
Auteurs : Samuel M. Goldman ; Freya Kamel ; G. Webster Ross ; Sarah A. Jewell ; Connie Marras ; Jane A. Hoppin ; David M. Umbach ; Grace S. Bhudhikanok ; Cheryl Meng ; Monica Korell ; Kathleen Comyns ; Robert A. Hauser ; Joseph Jankovic ; Stewart A. Factor ; Susan Bressman ; Kelly E. Lyons ; Dale P. Sandler ; J. William Langston ; Caroline M. TannerSource :
- Movement disorders : official journal of the Movement Disorder Society [ 0885-3185 ] ; 2014.
Abstract
Increased gut permeability, inflammation, and colonic α-synuclein pathology are present in early Parkinson’s disease (PD) and have been proposed to contribute to PD pathogenesis. Peptidoglycan is a structural component of the bacterial cell wall. Peptidoglycan recognition proteins (PGRPs) maintain healthy gut microbial flora by regulating the immune response to both commensal and harmful bacteria. We tested the hypothesis that variants in genes that encode PGRPs are associated with PD risk. Participants in two independent case-control studies were genotyped for 30 single-nucleotide polymorphisms (SNPs) in the four
Url:
DOI: 10.1002/mds.25895
PubMed: 24838182
PubMed Central: 4777298
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PMC:4777298Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Peptidoglycan Recognition Protein Genes and Risk of Parkinson’s Disease</title>
<author><name sortKey="Goldman, Samuel M" sort="Goldman, Samuel M" uniqKey="Goldman S" first="Samuel M." last="Goldman">Samuel M. Goldman</name>
<affiliation><nlm:aff id="A1">San Francisco Veterans Affairs Medical Center, San Francisco, California, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">University of California, San Francisco, San Francisco, California, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">The Parkinson’s Institute, Sunnyvale, California, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kamel, Freya" sort="Kamel, Freya" uniqKey="Kamel F" first="Freya" last="Kamel">Freya Kamel</name>
<affiliation><nlm:aff id="A4">Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, North Carolina, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ross, G Webster" sort="Ross, G Webster" uniqKey="Ross G" first="G. Webster" last="Ross">G. Webster Ross</name>
<affiliation><nlm:aff id="A5">Veterans Affairs Pacific Islands Health Care System, Honolulu, Hawaii, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Jewell, Sarah A" sort="Jewell, Sarah A" uniqKey="Jewell S" first="Sarah A." last="Jewell">Sarah A. Jewell</name>
<affiliation><nlm:aff id="A6">DZNE, German Center for Neurodegenerative Diseases, Bonn, Germany</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Marras, Connie" sort="Marras, Connie" uniqKey="Marras C" first="Connie" last="Marras">Connie Marras</name>
<affiliation><nlm:aff id="A7">Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hoppin, Jane A" sort="Hoppin, Jane A" uniqKey="Hoppin J" first="Jane A." last="Hoppin">Jane A. Hoppin</name>
<affiliation><nlm:aff id="A8">North Carolina State University, Raleigh, North Carolina, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Umbach, David M" sort="Umbach, David M" uniqKey="Umbach D" first="David M." last="Umbach">David M. Umbach</name>
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</affiliation>
</author>
<author><name sortKey="Bhudhikanok, Grace S" sort="Bhudhikanok, Grace S" uniqKey="Bhudhikanok G" first="Grace S." last="Bhudhikanok">Grace S. Bhudhikanok</name>
<affiliation><nlm:aff id="A3">The Parkinson’s Institute, Sunnyvale, California, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Meng, Cheryl" sort="Meng, Cheryl" uniqKey="Meng C" first="Cheryl" last="Meng">Cheryl Meng</name>
<affiliation><nlm:aff id="A3">The Parkinson’s Institute, Sunnyvale, California, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Korell, Monica" sort="Korell, Monica" uniqKey="Korell M" first="Monica" last="Korell">Monica Korell</name>
<affiliation><nlm:aff id="A3">The Parkinson’s Institute, Sunnyvale, California, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Comyns, Kathleen" sort="Comyns, Kathleen" uniqKey="Comyns K" first="Kathleen" last="Comyns">Kathleen Comyns</name>
<affiliation><nlm:aff id="A3">The Parkinson’s Institute, Sunnyvale, California, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hauser, Robert A" sort="Hauser, Robert A" uniqKey="Hauser R" first="Robert A." last="Hauser">Robert A. Hauser</name>
<affiliation><nlm:aff id="A10">University of South Florida, Tampa, Florida, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Jankovic, Joseph" sort="Jankovic, Joseph" uniqKey="Jankovic J" first="Joseph" last="Jankovic">Joseph Jankovic</name>
<affiliation><nlm:aff id="A11">Baylor College of Medicine, Houston, Texas, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Factor, Stewart A" sort="Factor, Stewart A" uniqKey="Factor S" first="Stewart A." last="Factor">Stewart A. Factor</name>
<affiliation><nlm:aff id="A12">Emory University School of Medicine, Atlanta, Georgia, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Bressman, Susan" sort="Bressman, Susan" uniqKey="Bressman S" first="Susan" last="Bressman">Susan Bressman</name>
<affiliation><nlm:aff id="A13">Beth Israel Medical Center, New York, New York, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Lyons, Kelly E" sort="Lyons, Kelly E" uniqKey="Lyons K" first="Kelly E." last="Lyons">Kelly E. Lyons</name>
<affiliation><nlm:aff id="A14">University of Kansas Medical Center, Kansas City, Kansas, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Sandler, Dale P" sort="Sandler, Dale P" uniqKey="Sandler D" first="Dale P." last="Sandler">Dale P. Sandler</name>
<affiliation><nlm:aff id="A4">Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, North Carolina, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Langston, J William" sort="Langston, J William" uniqKey="Langston J" first="J. William" last="Langston">J. William Langston</name>
<affiliation><nlm:aff id="A3">The Parkinson’s Institute, Sunnyvale, California, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Tanner, Caroline M" sort="Tanner, Caroline M" uniqKey="Tanner C" first="Caroline M." last="Tanner">Caroline M. Tanner</name>
<affiliation><nlm:aff id="A1">San Francisco Veterans Affairs Medical Center, San Francisco, California, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">University of California, San Francisco, San Francisco, California, USA</nlm:aff>
</affiliation>
</author>
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<date when="2014">2014</date>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Peptidoglycan Recognition Protein Genes and Risk of Parkinson’s Disease</title>
<author><name sortKey="Goldman, Samuel M" sort="Goldman, Samuel M" uniqKey="Goldman S" first="Samuel M." last="Goldman">Samuel M. Goldman</name>
<affiliation><nlm:aff id="A1">San Francisco Veterans Affairs Medical Center, San Francisco, California, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">University of California, San Francisco, San Francisco, California, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">The Parkinson’s Institute, Sunnyvale, California, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kamel, Freya" sort="Kamel, Freya" uniqKey="Kamel F" first="Freya" last="Kamel">Freya Kamel</name>
<affiliation><nlm:aff id="A4">Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, North Carolina, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ross, G Webster" sort="Ross, G Webster" uniqKey="Ross G" first="G. Webster" last="Ross">G. Webster Ross</name>
<affiliation><nlm:aff id="A5">Veterans Affairs Pacific Islands Health Care System, Honolulu, Hawaii, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Jewell, Sarah A" sort="Jewell, Sarah A" uniqKey="Jewell S" first="Sarah A." last="Jewell">Sarah A. Jewell</name>
<affiliation><nlm:aff id="A6">DZNE, German Center for Neurodegenerative Diseases, Bonn, Germany</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Marras, Connie" sort="Marras, Connie" uniqKey="Marras C" first="Connie" last="Marras">Connie Marras</name>
<affiliation><nlm:aff id="A7">Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hoppin, Jane A" sort="Hoppin, Jane A" uniqKey="Hoppin J" first="Jane A." last="Hoppin">Jane A. Hoppin</name>
<affiliation><nlm:aff id="A8">North Carolina State University, Raleigh, North Carolina, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Umbach, David M" sort="Umbach, David M" uniqKey="Umbach D" first="David M." last="Umbach">David M. Umbach</name>
<affiliation><nlm:aff id="A9">Biostatistics Branch, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, North Carolina, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Bhudhikanok, Grace S" sort="Bhudhikanok, Grace S" uniqKey="Bhudhikanok G" first="Grace S." last="Bhudhikanok">Grace S. Bhudhikanok</name>
<affiliation><nlm:aff id="A3">The Parkinson’s Institute, Sunnyvale, California, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Meng, Cheryl" sort="Meng, Cheryl" uniqKey="Meng C" first="Cheryl" last="Meng">Cheryl Meng</name>
<affiliation><nlm:aff id="A3">The Parkinson’s Institute, Sunnyvale, California, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Korell, Monica" sort="Korell, Monica" uniqKey="Korell M" first="Monica" last="Korell">Monica Korell</name>
<affiliation><nlm:aff id="A3">The Parkinson’s Institute, Sunnyvale, California, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Comyns, Kathleen" sort="Comyns, Kathleen" uniqKey="Comyns K" first="Kathleen" last="Comyns">Kathleen Comyns</name>
<affiliation><nlm:aff id="A3">The Parkinson’s Institute, Sunnyvale, California, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hauser, Robert A" sort="Hauser, Robert A" uniqKey="Hauser R" first="Robert A." last="Hauser">Robert A. Hauser</name>
<affiliation><nlm:aff id="A10">University of South Florida, Tampa, Florida, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Jankovic, Joseph" sort="Jankovic, Joseph" uniqKey="Jankovic J" first="Joseph" last="Jankovic">Joseph Jankovic</name>
<affiliation><nlm:aff id="A11">Baylor College of Medicine, Houston, Texas, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Factor, Stewart A" sort="Factor, Stewart A" uniqKey="Factor S" first="Stewart A." last="Factor">Stewart A. Factor</name>
<affiliation><nlm:aff id="A12">Emory University School of Medicine, Atlanta, Georgia, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Bressman, Susan" sort="Bressman, Susan" uniqKey="Bressman S" first="Susan" last="Bressman">Susan Bressman</name>
<affiliation><nlm:aff id="A13">Beth Israel Medical Center, New York, New York, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Lyons, Kelly E" sort="Lyons, Kelly E" uniqKey="Lyons K" first="Kelly E." last="Lyons">Kelly E. Lyons</name>
<affiliation><nlm:aff id="A14">University of Kansas Medical Center, Kansas City, Kansas, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Sandler, Dale P" sort="Sandler, Dale P" uniqKey="Sandler D" first="Dale P." last="Sandler">Dale P. Sandler</name>
<affiliation><nlm:aff id="A4">Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, North Carolina, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Langston, J William" sort="Langston, J William" uniqKey="Langston J" first="J. William" last="Langston">J. William Langston</name>
<affiliation><nlm:aff id="A3">The Parkinson’s Institute, Sunnyvale, California, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Tanner, Caroline M" sort="Tanner, Caroline M" uniqKey="Tanner C" first="Caroline M." last="Tanner">Caroline M. Tanner</name>
<affiliation><nlm:aff id="A1">San Francisco Veterans Affairs Medical Center, San Francisco, California, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">University of California, San Francisco, San Francisco, California, USA</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title>
<idno type="ISSN">0885-3185</idno>
<idno type="eISSN">1531-8257</idno>
<imprint><date when="2014">2014</date>
</imprint>
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<front><div type="abstract" xml:lang="en"><p id="P1">Increased gut permeability, inflammation, and colonic α-synuclein pathology are present in early Parkinson’s disease (PD) and have been proposed to contribute to PD pathogenesis. Peptidoglycan is a structural component of the bacterial cell wall. Peptidoglycan recognition proteins (PGRPs) maintain healthy gut microbial flora by regulating the immune response to both commensal and harmful bacteria. We tested the hypothesis that variants in genes that encode PGRPs are associated with PD risk. Participants in two independent case-control studies were genotyped for 30 single-nucleotide polymorphisms (SNPs) in the four <italic>PGLYRP</italic>
genes. Using logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusted for potential confounding variables, we conducted analyses in each study, separately and pooled. One SNP failed the assay, and three had little to no variation. The ORs were similar in both study populations. In pooled analyses, three of seven <italic>PGLYRP2</italic>
SNPs (rs3813135, rs733731, rs892145), one of five <italic>PGLYRP3</italic>
SNPs (rs2987763), and six of nine <italic>PGLYRP4</italic>
SNPs (rs10888557, rs12063091, rs3006440, rs3006448, rs3006458, and rs3014864) were significantly associated with PD risk. Association was strongest for <italic>PGLYRP4</italic>
5’untranslated region (UTR) SNP rs10888557 (GG reference, CG OR 0.6 [95%CI 0.4–0.9], CC OR 0.15 [95%CI 0.04–0.6]; log-additive <italic>P</italic>
-trend, 0.0004). Common variants in <italic>PGLYRP</italic>
genes are associated with PD risk in two independent studies. These results require replication, but they are consistent with hypotheses of a causative role for the gut microbiota and gastrointestinal immune response in PD.</p>
</div>
</front>
</TEI>
<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">8610688</journal-id>
<journal-id journal-id-type="pubmed-jr-id">5937</journal-id>
<journal-id journal-id-type="nlm-ta">Mov Disord</journal-id>
<journal-id journal-id-type="iso-abbrev">Mov. Disord.</journal-id>
<journal-title-group><journal-title>Movement disorders : official journal of the Movement Disorder Society</journal-title>
</journal-title-group>
<issn pub-type="ppub">0885-3185</issn>
<issn pub-type="epub">1531-8257</issn>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">24838182</article-id>
<article-id pub-id-type="pmc">4777298</article-id>
<article-id pub-id-type="doi">10.1002/mds.25895</article-id>
<article-id pub-id-type="manuscript">NIHMS583594</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Peptidoglycan Recognition Protein Genes and Risk of Parkinson’s Disease</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Goldman</surname>
<given-names>Samuel M.</given-names>
</name>
<degrees>MD, MPH</degrees>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="aff" rid="A3">3</xref>
<xref ref-type="corresp" rid="cor1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kamel</surname>
<given-names>Freya</given-names>
</name>
<degrees>PhD</degrees>
<xref ref-type="aff" rid="A4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ross</surname>
<given-names>G. Webster</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="A5">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Jewell</surname>
<given-names>Sarah A.</given-names>
</name>
<degrees>MD, MPH</degrees>
<xref ref-type="aff" rid="A6">6</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Marras</surname>
<given-names>Connie</given-names>
</name>
<degrees>MD, PhD</degrees>
<xref ref-type="aff" rid="A7">7</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hoppin</surname>
<given-names>Jane A.</given-names>
</name>
<degrees>ScD</degrees>
<xref ref-type="aff" rid="A8">8</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Umbach</surname>
<given-names>David M.</given-names>
</name>
<degrees>PhD</degrees>
<xref ref-type="aff" rid="A9">9</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Bhudhikanok</surname>
<given-names>Grace S.</given-names>
</name>
<degrees>PhD</degrees>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Meng</surname>
<given-names>Cheryl</given-names>
</name>
<degrees>MS</degrees>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Korell</surname>
<given-names>Monica</given-names>
</name>
<degrees>MPH</degrees>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Comyns</surname>
<given-names>Kathleen</given-names>
</name>
<degrees>MPH</degrees>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hauser</surname>
<given-names>Robert A.</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="A10">10</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Jankovic</surname>
<given-names>Joseph</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="A11">11</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Factor</surname>
<given-names>Stewart A.</given-names>
</name>
<degrees>DO</degrees>
<xref ref-type="aff" rid="A12">12</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Bressman</surname>
<given-names>Susan</given-names>
</name>
<degrees>DMD</degrees>
<xref ref-type="aff" rid="A13">13</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Lyons</surname>
<given-names>Kelly E.</given-names>
</name>
<degrees>PhD</degrees>
<xref ref-type="aff" rid="A14">14</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Sandler</surname>
<given-names>Dale P.</given-names>
</name>
<degrees>PhD</degrees>
<xref ref-type="aff" rid="A4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Langston</surname>
<given-names>J. William</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Tanner</surname>
<given-names>Caroline M.</given-names>
</name>
<degrees>MD, PhD</degrees>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
</contrib-group>
<aff id="A1"><label>1</label>
San Francisco Veterans Affairs Medical Center, San Francisco, California, USA</aff>
<aff id="A2"><label>2</label>
University of California, San Francisco, San Francisco, California, USA</aff>
<aff id="A3"><label>3</label>
The Parkinson’s Institute, Sunnyvale, California, USA</aff>
<aff id="A4"><label>4</label>
Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, North Carolina, USA</aff>
<aff id="A5"><label>5</label>
Veterans Affairs Pacific Islands Health Care System, Honolulu, Hawaii, USA</aff>
<aff id="A6"><label>6</label>
DZNE, German Center for Neurodegenerative Diseases, Bonn, Germany</aff>
<aff id="A7"><label>7</label>
Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada</aff>
<aff id="A8"><label>8</label>
North Carolina State University, Raleigh, North Carolina, USA</aff>
<aff id="A9"><label>9</label>
Biostatistics Branch, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, North Carolina, USA</aff>
<aff id="A10"><label>10</label>
University of South Florida, Tampa, Florida, USA</aff>
<aff id="A11"><label>11</label>
Baylor College of Medicine, Houston, Texas, USA</aff>
<aff id="A12"><label>12</label>
Emory University School of Medicine, Atlanta, Georgia, USA</aff>
<aff id="A13"><label>13</label>
Beth Israel Medical Center, New York, New York, USA</aff>
<aff id="A14"><label>14</label>
University of Kansas Medical Center, Kansas City, Kansas, USA</aff>
<author-notes><corresp id="cor1"><label>*</label>
<bold>Correspondence to:</bold>
Samuel M. Goldman, MD, MPH, San Francisco Veterans Affairs Medical Center, 4150 Clement Street, PADRECC—127P, San Francisco, CA, <email>samuel.goldman@ucsf.edu</email>
</corresp>
</author-notes>
<pub-date pub-type="nihms-submitted"><day>11</day>
<month>6</month>
<year>2014</year>
</pub-date>
<pub-date pub-type="epub"><day>17</day>
<month>5</month>
<year>2014</year>
</pub-date>
<pub-date pub-type="ppub"><month>8</month>
<year>2014</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>03</day>
<month>3</month>
<year>2016</year>
</pub-date>
<volume>29</volume>
<issue>9</issue>
<fpage>1171</fpage>
<lpage>1180</lpage>
<pmc-comment>elocation-id from pubmed: 10.1002/mds.25895</pmc-comment>
<abstract><p id="P1">Increased gut permeability, inflammation, and colonic α-synuclein pathology are present in early Parkinson’s disease (PD) and have been proposed to contribute to PD pathogenesis. Peptidoglycan is a structural component of the bacterial cell wall. Peptidoglycan recognition proteins (PGRPs) maintain healthy gut microbial flora by regulating the immune response to both commensal and harmful bacteria. We tested the hypothesis that variants in genes that encode PGRPs are associated with PD risk. Participants in two independent case-control studies were genotyped for 30 single-nucleotide polymorphisms (SNPs) in the four <italic>PGLYRP</italic>
genes. Using logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusted for potential confounding variables, we conducted analyses in each study, separately and pooled. One SNP failed the assay, and three had little to no variation. The ORs were similar in both study populations. In pooled analyses, three of seven <italic>PGLYRP2</italic>
SNPs (rs3813135, rs733731, rs892145), one of five <italic>PGLYRP3</italic>
SNPs (rs2987763), and six of nine <italic>PGLYRP4</italic>
SNPs (rs10888557, rs12063091, rs3006440, rs3006448, rs3006458, and rs3014864) were significantly associated with PD risk. Association was strongest for <italic>PGLYRP4</italic>
5’untranslated region (UTR) SNP rs10888557 (GG reference, CG OR 0.6 [95%CI 0.4–0.9], CC OR 0.15 [95%CI 0.04–0.6]; log-additive <italic>P</italic>
-trend, 0.0004). Common variants in <italic>PGLYRP</italic>
genes are associated with PD risk in two independent studies. These results require replication, but they are consistent with hypotheses of a causative role for the gut microbiota and gastrointestinal immune response in PD.</p>
</abstract>
<kwd-group><kwd>Parkinson’s disease</kwd>
<kwd>peptidoglycan</kwd>
<kwd>PGLYRP</kwd>
<kwd>microbiome</kwd>
<kwd>gut</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
</record>
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