<scp>GPNMB</scp> Biomarker Levels in <scp><i>GBA1</i></scp> Carriers with Lewy Body Disorders-Reference-Cited by-同舟云学术

GPNMB Biomarker Levels in GBA1 Carriers with Lewy Body Disorders

Published:2024-04-12 Issue:6 Volume:39 Page:1065-1070
ISSN:0885-3185
Container-title:Movement Disorders
language:en
Short-container-title:Movement Disorders

Author:

Brody Eliza M.¹,Seo Yunji¹,Suh EunRan²,Amari Noor¹,Hartstone Whitney G.¹,Skrinak R. Tyler¹,Zhang Hanwen¹,Diaz‐Ortiz Maria E.¹,Weintraub Daniel³⁴^ORCID,Tropea Thomas F.¹,Van Deerlin Vivianna M.²,Chen‐Plotkin Alice S.¹³⁴^ORCID

Affiliation:

1. Department of Neurology Perelman School of Medicine, University of Pennsylvania Philadelphia Pennsylvania USA

2. Department of Pathology and Laboratory Medicine Perelman School of Medicine, University of Pennsylvania Philadelphia Pennsylvania USA

3. Department of Psychiatry Perelman School of Medicine, University of Pennsylvania Philadelphia Pennsylvania USA

4. Parkinson's Disease Research, Education, and Clinical Center Philadelphia Veterans Affairs Medical Center Philadelphia Pennsylvania USA

Abstract

AbstractBackgroundThe GPNMB single‐nucleotide polymorphism rs199347 and GBA1 variants both associate with Lewy body disorder (LBD) risk. GPNMB encodes glycoprotein nonmetastatic melanoma protein B (GPNMB), a biomarker for GBA1‐associated Gaucher's disease.ObjectiveThe aim of this study was to determine whether GPNMB levels (1) differ in LBD with and without GBA1 variants and (2) associate with rs199347 genotype.MethodsWe quantified GPNMB levels in plasma and cerebrospinal fluid (CSF) from 124 individuals with LBD with one GBA1 variant (121 plasma, 14 CSF), 631 individuals with LBD without GBA1 variants (626 plasma, 41 CSF), 9 neurologically normal individuals with one GBA1 variant (plasma), and 2 individuals with two GBA1 variants (plasma). We tested for associations between GPNMB levels and rs199347 or GBA1 status.ResultsGPNMB levels associate with rs199347 genotype in plasma (P = 0.022) and CSF (P = 0.007), but not with GBA1 status.Conclusionsrs199347 is a protein quantitative trait locus for GPNMB. GPNMB levels are unaltered in individuals carrying one GBA1 variant. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Funder

National Institute of Neurological Disorders and Stroke

National Institute on Aging

Publisher

Wiley

Reference29 articles.

1. Molecular genetics of Parkinson’s disease: Contributions and global trends

2. Identification of novel risk loci, causal insights, and heritable risk for Parkinson's disease: a meta-analysis of genome-wide association studies

3. GPNMB confers risk for Parkinson’s disease through interaction with α-synuclein

4. Increased brain expression of GPNMB is associated with genome wide significant risk for Parkinson’s disease on chromosome 7p15.3

5. The glycoprotein GPNMB is selectively elevated in the substantia nigra of Parkinson's disease patients and increases after lysosomal stress