Peptidoglycan recognition protein genes and risk of Parkinson's disease.
Identifieur interne : 000481 ( Main/Exploration ); précédent : 000480; suivant : 000482Peptidoglycan recognition protein genes and risk of Parkinson's disease.
Auteurs : Samuel M. Goldman [États-Unis] ; 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 [États-Unis] ; 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 [ 1531-8257 ] ; 2014.
English descriptors
- KwdEn :
- Adult, Aged, Aged, 80 and over, Carrier Proteins (genetics), Case-Control Studies, Female, Genetic Association Studies, Genetic Predisposition to Disease (genetics), Genotype, Humans, Logistic Models, Male, Microbiota (genetics), Middle Aged, Odds Ratio, Parkinson Disease (genetics), Polymorphism, Single Nucleotide (genetics).
- MESH :
- chemical , genetics : Carrier Proteins.
- genetics : Genetic Predisposition to Disease, Microbiota, Parkinson Disease, Polymorphism, Single Nucleotide.
- Adult, Aged, Aged, 80 and over, Case-Control Studies, Female, Genetic Association Studies, Genotype, Humans, Logistic Models, Male, Middle Aged, Odds Ratio.
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 PGLYRP 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 PGLYRP2 SNPs (rs3813135, rs733731, rs892145), one of five PGLYRP3 SNPs (rs2987763), and six of nine PGLYRP4 SNPs (rs10888557, rs12063091, rs3006440, rs3006448, rs3006458, and rs3014864) were significantly associated with PD risk. Association was strongest for PGLYRP4 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 P-trend, 0.0004). Common variants in PGLYRP 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.
DOI: 10.1002/mds.25895
PubMed: 24838182
Affiliations:
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Goldman</name><affiliation wicri:level="2"><nlm:affiliation>San Francisco Veterans Affairs Medical Center, San Francisco, California, USA; University of California, San Francisco, San Francisco, California, USA; The Parkinson's Institute, Sunnyvale, California, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>San Francisco Veterans Affairs Medical Center, San Francisco, California, USA; University of California, San Francisco, San Francisco, California, USA; The Parkinson's Institute, Sunnyvale, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Kamel, Freya" sort="Kamel, Freya" uniqKey="Kamel F" first="Freya" last="Kamel">Freya Kamel</name></author><author><name sortKey="Ross, G Webster" sort="Ross, G Webster" uniqKey="Ross G" first="G Webster" last="Ross">G Webster Ross</name></author><author><name sortKey="Jewell, Sarah A" sort="Jewell, Sarah A" uniqKey="Jewell S" first="Sarah A" last="Jewell">Sarah A. Jewell</name></author><author><name sortKey="Marras, Connie" sort="Marras, Connie" uniqKey="Marras C" first="Connie" last="Marras">Connie Marras</name></author><author><name sortKey="Hoppin, Jane A" sort="Hoppin, Jane A" uniqKey="Hoppin J" first="Jane A" last="Hoppin">Jane A. Hoppin</name></author><author><name sortKey="Umbach, David M" sort="Umbach, David M" uniqKey="Umbach D" first="David M" last="Umbach">David M. Umbach</name></author><author><name sortKey="Bhudhikanok, Grace S" sort="Bhudhikanok, Grace S" uniqKey="Bhudhikanok G" first="Grace S" last="Bhudhikanok">Grace S. 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Tanner</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2014">2014</date><idno type="RBID">pubmed:24838182</idno><idno type="pmid">24838182</idno><idno type="doi">10.1002/mds.25895</idno><idno type="wicri:Area/PubMed/Corpus">000499</idno><idno type="wicri:Area/PubMed/Curation">000499</idno><idno type="wicri:Area/PubMed/Checkpoint">000486</idno><idno type="wicri:Area/Ncbi/Merge">004000</idno><idno type="wicri:Area/Ncbi/Curation">004000</idno><idno type="wicri:Area/Ncbi/Checkpoint">004000</idno><idno type="wicri:Area/Main/Merge">000481</idno><idno type="wicri:Area/Main/Curation">000481</idno><idno type="wicri:Area/Main/Exploration">000481</idno></publicationStmt><sourceDesc><biblStruct><analytic><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 wicri:level="2"><nlm:affiliation>San Francisco Veterans Affairs Medical Center, San Francisco, California, USA; University of California, San Francisco, San Francisco, California, USA; The Parkinson's Institute, Sunnyvale, California, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>San Francisco Veterans Affairs Medical Center, San Francisco, California, USA; University of California, San Francisco, San Francisco, California, USA; The Parkinson's Institute, Sunnyvale, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Kamel, Freya" sort="Kamel, Freya" uniqKey="Kamel F" first="Freya" last="Kamel">Freya Kamel</name></author><author><name sortKey="Ross, G Webster" sort="Ross, G Webster" uniqKey="Ross G" first="G Webster" last="Ross">G Webster Ross</name></author><author><name sortKey="Jewell, Sarah A" sort="Jewell, Sarah A" uniqKey="Jewell S" first="Sarah A" last="Jewell">Sarah A. Jewell</name></author><author><name sortKey="Marras, Connie" sort="Marras, Connie" uniqKey="Marras C" first="Connie" last="Marras">Connie Marras</name></author><author><name sortKey="Hoppin, Jane A" sort="Hoppin, Jane A" uniqKey="Hoppin J" first="Jane A" last="Hoppin">Jane A. Hoppin</name></author><author><name sortKey="Umbach, David M" sort="Umbach, David M" uniqKey="Umbach D" first="David M" last="Umbach">David M. Umbach</name></author><author><name sortKey="Bhudhikanok, Grace S" sort="Bhudhikanok, Grace S" uniqKey="Bhudhikanok G" first="Grace S" last="Bhudhikanok">Grace S. Bhudhikanok</name></author><author><name sortKey="Meng, Cheryl" sort="Meng, Cheryl" uniqKey="Meng C" first="Cheryl" last="Meng">Cheryl Meng</name></author><author><name sortKey="Korell, Monica" sort="Korell, Monica" uniqKey="Korell M" first="Monica" last="Korell">Monica Korell</name></author><author><name sortKey="Comyns, Kathleen" sort="Comyns, Kathleen" uniqKey="Comyns K" first="Kathleen" last="Comyns">Kathleen Comyns</name></author><author><name sortKey="Hauser, Robert A" sort="Hauser, Robert A" uniqKey="Hauser R" first="Robert A" last="Hauser">Robert A. Hauser</name></author><author><name sortKey="Jankovic, Joseph" sort="Jankovic, Joseph" uniqKey="Jankovic J" first="Joseph" last="Jankovic">Joseph Jankovic</name><affiliation><country>États-Unis</country><placeName><settlement type="city">Houston</settlement><region type="state">Texas</region></placeName><orgName type="university" n="3">Baylor College of Medicine</orgName></affiliation></author><author><name sortKey="Factor, Stewart A" sort="Factor, Stewart A" uniqKey="Factor S" first="Stewart A" last="Factor">Stewart A. Factor</name></author><author><name sortKey="Bressman, Susan" sort="Bressman, Susan" uniqKey="Bressman S" first="Susan" last="Bressman">Susan Bressman</name></author><author><name sortKey="Lyons, Kelly E" sort="Lyons, Kelly E" uniqKey="Lyons K" first="Kelly E" last="Lyons">Kelly E. Lyons</name></author><author><name sortKey="Sandler, Dale P" sort="Sandler, Dale P" uniqKey="Sandler D" first="Dale P" last="Sandler">Dale P. Sandler</name></author><author><name sortKey="Langston, J William" sort="Langston, J William" uniqKey="Langston J" first="J William" last="Langston">J William Langston</name></author><author><name sortKey="Tanner, Caroline M" sort="Tanner, Caroline M" uniqKey="Tanner C" first="Caroline M" last="Tanner">Caroline M. Tanner</name></author></analytic><series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title><idno type="eISSN">1531-8257</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Aged</term><term>Aged, 80 and over</term><term>Carrier Proteins (genetics)</term><term>Case-Control Studies</term><term>Female</term><term>Genetic Association Studies</term><term>Genetic Predisposition to Disease (genetics)</term><term>Genotype</term><term>Humans</term><term>Logistic Models</term><term>Male</term><term>Microbiota (genetics)</term><term>Middle Aged</term><term>Odds Ratio</term><term>Parkinson Disease (genetics)</term><term>Polymorphism, Single Nucleotide (genetics)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Carrier Proteins</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Genetic Predisposition to Disease</term><term>Microbiota</term><term>Parkinson Disease</term><term>Polymorphism, Single Nucleotide</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Aged</term><term>Aged, 80 and over</term><term>Case-Control Studies</term><term>Female</term><term>Genetic Association Studies</term><term>Genotype</term><term>Humans</term><term>Logistic Models</term><term>Male</term><term>Middle Aged</term><term>Odds Ratio</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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 PGLYRP 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 PGLYRP2 SNPs (rs3813135, rs733731, rs892145), one of five PGLYRP3 SNPs (rs2987763), and six of nine PGLYRP4 SNPs (rs10888557, rs12063091, rs3006440, rs3006448, rs3006458, and rs3014864) were significantly associated with PD risk. Association was strongest for PGLYRP4 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 P-trend, 0.0004). Common variants in PGLYRP 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.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Californie</li><li>Texas</li></region><settlement><li>Houston</li></settlement><orgName><li>Baylor College of Medicine</li></orgName></list><tree><noCountry><name sortKey="Bhudhikanok, Grace S" sort="Bhudhikanok, Grace S" uniqKey="Bhudhikanok G" first="Grace S" last="Bhudhikanok">Grace S. Bhudhikanok</name><name sortKey="Bressman, Susan" sort="Bressman, Susan" uniqKey="Bressman S" first="Susan" last="Bressman">Susan Bressman</name><name sortKey="Comyns, Kathleen" sort="Comyns, Kathleen" uniqKey="Comyns K" first="Kathleen" last="Comyns">Kathleen Comyns</name><name sortKey="Factor, Stewart A" sort="Factor, Stewart A" uniqKey="Factor S" first="Stewart A" last="Factor">Stewart A. Factor</name><name sortKey="Hauser, Robert A" sort="Hauser, Robert A" uniqKey="Hauser R" first="Robert A" last="Hauser">Robert A. Hauser</name><name sortKey="Hoppin, Jane A" sort="Hoppin, Jane A" uniqKey="Hoppin J" first="Jane A" last="Hoppin">Jane A. Hoppin</name><name sortKey="Jewell, Sarah A" sort="Jewell, Sarah A" uniqKey="Jewell S" first="Sarah A" last="Jewell">Sarah A. Jewell</name><name sortKey="Kamel, Freya" sort="Kamel, Freya" uniqKey="Kamel F" first="Freya" last="Kamel">Freya Kamel</name><name sortKey="Korell, Monica" sort="Korell, Monica" uniqKey="Korell M" first="Monica" last="Korell">Monica Korell</name><name sortKey="Langston, J William" sort="Langston, J William" uniqKey="Langston J" first="J William" last="Langston">J William Langston</name><name sortKey="Lyons, Kelly E" sort="Lyons, Kelly E" uniqKey="Lyons K" first="Kelly E" last="Lyons">Kelly E. Lyons</name><name sortKey="Marras, Connie" sort="Marras, Connie" uniqKey="Marras C" first="Connie" last="Marras">Connie Marras</name><name sortKey="Meng, Cheryl" sort="Meng, Cheryl" uniqKey="Meng C" first="Cheryl" last="Meng">Cheryl Meng</name><name sortKey="Ross, G Webster" sort="Ross, G Webster" uniqKey="Ross G" first="G Webster" last="Ross">G Webster Ross</name><name sortKey="Sandler, Dale P" sort="Sandler, Dale P" uniqKey="Sandler D" first="Dale P" last="Sandler">Dale P. Sandler</name><name sortKey="Tanner, Caroline M" sort="Tanner, Caroline M" uniqKey="Tanner C" first="Caroline M" last="Tanner">Caroline M. Tanner</name><name sortKey="Umbach, David M" sort="Umbach, David M" uniqKey="Umbach D" first="David M" last="Umbach">David M. Umbach</name></noCountry><country name="États-Unis"><region name="Californie"><name sortKey="Goldman, Samuel M" sort="Goldman, Samuel M" uniqKey="Goldman S" first="Samuel M" last="Goldman">Samuel M. Goldman</name></region><name sortKey="Jankovic, Joseph" sort="Jankovic, Joseph" uniqKey="Jankovic J" first="Joseph" last="Jankovic">Joseph Jankovic</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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