Peptidoglycan recognition protein genes and risk of Parkinson's disease |
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| Authors: | Samuel M Goldman MD MPH Freya Kamel PhD G Webster Ross MD Sarah A Jewell MD MPH Connie Marras MD PhD Jane A Hoppin ScD David M Umbach PhD Grace S Bhudhikanok PhD Cheryl Meng MS Monica Korell MPH Kathleen Comyns MPH Robert A Hauser MD Joseph Jankovic MD Stewart A Factor DO Susan Bressman MD Kelly E Lyons PhD Dale P Sandler PhD J William Langston MD Caroline M Tanner MD PhD |
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| Institution: | 1. San Francisco Veterans Affairs Medical Center, , San Francisco, California, USA;2. University of California, San Francisco, , San Francisco, California, USA;3. The Parkinson's Institute, , Sunnyvale, California, USA;4. Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, , North Carolina, USA;5. Veterans Affairs Pacific Islands Health Care System, , Honolulu, Hawaii, USA;6. DZNE, German Center for Neurodegenerative Diseases, , Bonn, Germany;7. Toronto Western Hospital, University of Toronto, , Toronto, Ontario, Canada;8. North Carolina State University, , Raleigh, North Carolina, USA;9. Biostatistics Branch, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, , North Carolina, USA;10. University of South Florida, , Tampa, Florida, USA;11. Baylor College of Medicine, , Houston, Texas, USA;12. Emory University School of Medicine, , Atlanta, Georgia, USA;13. Beth Israel Medical Center, , New York, New York, USA;14. University of Kansas Medical Center, , Kansas City, Kansas, USA |
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| 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. © 2014 International Parkinson and Movement Disorder Society |
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| Keywords: | Parkinson's disease peptidoglycan PGLYRP microbiome gut |
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