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. 2024 Jun;39(6):1065-1070.
doi: 10.1002/mds.29773. Epub 2024 Apr 12.

GPNMB Biomarker Levels in GBA1 Carriers with Lewy Body Disorders

Eliza M Brody  1 , Yunji Seo  1 , EunRan Suh  2 , Noor Amari  1 , Whitney G Hartstone  1 , R Tyler Skrinak  1 , Hanwen Zhang  1 , Maria E Diaz-Ortiz  1 , Daniel Weintraub  3   4 , Thomas F Tropea  1 , Vivianna M Van Deerlin  2 , Alice S Chen-Plotkin  1   3   4
Affiliations

GPNMB Biomarker Levels in GBA1 Carriers with Lewy Body Disorders

Eliza M Brody et al. Mov Disord. 2024 Jun.

Abstract

Background: The 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.

Objective: The 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.

Methods: We 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.

Results: GPNMB levels associate with rs199347 genotype in plasma (P = 0.022) and CSF (P = 0.007), but not with GBA1 status.

Conclusions: rs199347 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.

Keywords: GBA; GBA1; GPNMB; Parkinson's disease; biomarker; glycoprotein nonmetastatic melanoma protein B.

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Figures

Figure 1.
Figure 1.. GPNMB levels are not associated with GBA1 status.
Plasma and/or CSF from 766 individuals were tested for GPNMB levels. (A) Plasma or (B) CSF GPNMB from GBA1 carriers and non-carriers with LBD are compared. Mann-Whitney U-test p-value is shown. (C) Plasma or (D) CSF GPNMB levels from LBD individuals are stratified by rs199347 genotype and GBA1 variant class. P-values for individual effects by two-way ANOVA are shown. (E) Among carriers of one GBA1 N409S mutations, plasma levels for GPNMB do not differ comparing neurologically normal (NC) individuals to LBD individuals. However, LBD individuals with two GBA1 N409S mutations show previously reported increases in GPNMB levels. Mann-Whitney U-test p-value comparing NC and LBD is shown. (A-E) DLB and PNOS individuals (bolder color) admix with PD individuals (pastel shade). Lines and error bars display median and 95% confidence interval (CI), respectively.
See this image and copyright information in PMC

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