Abstract Details

Title Parkinson's Disease Risk Is Associated with Variants in Genes That Bind Bacterial Cell-Wall Peptidoglycan

Topic Movement Disorders

Presentation(s) P05 - (-)

Poster/Presentation
Number 051

Objective

Background BACKGROUND: Peptidoglycan is a structural component of the bacterial cell wall, which binds recognition proteins encoded by PGLYRP genes. Peptidoglycan-recognition-proteins play a role in maintenance of healthy gut microbial flora and immune system activation. Lipopolysaccharide (LPS) from the cell membrane of gram negative bacteria has been shown to induce a parkinsonian syndrome in animal models, but peptidoglycan has not been well-studied.

Design/Methods DESIGN/METHODS: DNA was obtained from 385 PD cases and 159 matched controls from eight North American movement disorders centers. Subjects were genotyped for 30 tag single nucleotide polymorphisms (SNPs) in the 4 PGLYRPs genes. After assessing Hardy-Weinberg equilibrium, we used logistic regression to estimate odds ratios (ORs) adjusted for gender, age, race and smoking.

Results RESULTS: 22 SNPs had sufficient variation to analyze. 1 of 5 PGLYRP3 SNPs and 6 of 9 PGLYRP4 SNPs were significantly associated with PD risk. For rs2987763 in the flanking_5'UTR of PGLYRP3, ORs and 95%CIs were: TT ref, AT 1.2 (0.8-1.8), AA 1.8 (1.02-3.1), p=0.044. For PGLYRP4, associations were strongest for rs10888557 in the flanking_5'UTR: CC ref, CG 3.6 (0.8-15.2), GG 5.2 (1.3-21.2), p=0.01; and rs3006458, a missense SNP in exon 1: TT ref, TG 2.1 (0.8-5.6), GG 2.7 (1.02-6.9), p= 0.04.

Conclusions CONCLUSIONS: Common variants in PGLYRP genes are associated with PD risk. Intestinal abnormalities, altered gut flora and immune activation have all been proposed to contribute to PD pathogenesis, but information is limited. Studying peptidoglycan exposure and interaction with PGLYRP variants may provide new insights into these associations.

Authors/Disclosures
Samuel Goldman, MD, MPH PRESENTER	Dr. Goldman has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Littlepage Booth Leckman. The institution of Dr. Goldman has received research support from Michael J Fox Foundation. The institution of Dr. Goldman has received research support from US Department of Defense. The institution of Dr. Goldman has received research support from US Veterans Administration. The institution of Dr. Goldman has received research support from National Institutes of Health. The institution of Dr. Goldman has received research support from Health Resources and Services Administration. The institution of Dr. Goldman has received research support from American Academy of Pediatrics. Dr. Goldman has received personal compensation in the range of $100,000-$499,999 for serving as a Professor with University of California San Francisco. Dr. Goldman has received personal compensation in the range of $100,000-$499,999 for serving as a Staff Physician with San Francisco Veterans Affairs Health Care System.
	No disclosure on file
	No disclosure on file
Web Ross, MD (Pacific Health Research and ��ɫ�� Institute)	The institution of Dr. Ross has received research support from Michael J Fox Foundation. The institution of Dr. Ross has received research support from NIH.
Anabel R. Chade, MD	No disclosure on file
Meike Kasten, MD	No disclosure on file
	No disclosure on file
Grace S. Bhudhikanok, PhD	No disclosure on file
	No disclosure on file
Monica Korell, MPH	Ms. Korell has nothing to disclose.
J W. Langston, MD	No disclosure on file
Caroline M. Tanner, MD, PhD, FAAN (University of California San Francisco, Weill Institute for Neurosciences)	Dr. Tanner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Evidera. Dr. Tanner has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Neurocrine. Dr. Tanner has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Jazz Pharmaceuticals/Cavion. Dr. Tanner has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bial . Dr. Tanner has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Supernus. Dr. Tanner has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche Genentech. The institution of Dr. Tanner has received research support from Gateway LLC. The institution of Dr. Tanner has received research support from Roche\Genentech. The institution of Dr. Tanner has received research support from Michael J Fox Foundation . The institution of Dr. Tanner has received research support from National Institute of Health . The institution of Dr. Tanner has received research support from Department of Defense. Dr. Tanner has received personal compensation in the range of $500-$4,999 for serving as a Faculty, CME presentation with Medscape /WebND.

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