Peptidoglycan recognition protein genes and risk of Parkinson's disease


  • Funding agencies: This study was supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences, NIEHS (grants Z01-ES044007 and Z01-ES049030), NCI (grant Z01-CP010119), NIEHS grants R01-ES10803 and U54 ES012077, the Michael J. Fox Foundation, Parkinson's Unity Walk, and James and Sharron Clark. SEARCH was supported by an unrestricted grant from a group of current and former manufacturers of welding consumables awarded to The Parkinson's Institute.

  • Relevant conflicts of interest/financial disclosures: R.A.H. and S.M.G. received fees as expert witnesses from a group of current and former manufacturers of welding consumables.

  • Full financial disclosures and author roles may be found in the online version of this article.


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