Down-regulation of B cell-related genes in peripheral blood leukocytes of Parkinson's disease patients with and without GBA mutations

Hila Kobo, Anat Bar-Shira, Dvir Dahary, Ziv Gan-Or, Anat Mirelman, Orly Goldstein, Nir Giladi, Avi Orr-Urtreger*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Parkinson's disease (PD) is a common neurodegenerative disorder, caused by aging, genetic and environmental factors. Many genes and genetic loci have been implicated in autosomal dominant and recessive PD, among them SNCA, LRRK2, GBA, Parkin, DJ1 and PINK1.Mutations in the LRRK2 and GBA genes are especially common among PD patients of Ashkenazi-Jewish (AJ) origin, accounting for over a third of the patient population. We aimed to identify genes and cellular pathways that may be involved in GBA-associated PD. Whole genome expression analysis was performed using peripheral blood leukocytes (PBLs) of PD patients with mutations in the GBA gene (PD-GBA, n = 59) compared to healthy controls (n = 59). Significant expression changes were detected in 26 genes, most of themwere down-regulated in patients and annotated to B cell or immune-related functions. The expression levels of five membrane-bound B cell genes (FCRL1, CD19, CD22, CD79A and CD180) were further analyzed in four distinct populations: (1) Healthy controls (n=20), (2) PD-GBA (n=20), (3) PD patients who do not carry LRRK2 or GBA mutations (PD-NC, n=20), (4) Asymptomatic 1st degree family members,with (n= 15) orwithout (n=15) GBAmutations. In qRT-PCR analysis, all five geneswere down-regulated in patients (PDGBA and PD-NC) compared to controls. These changes in expression were not observed when comparing family members who carry GBA mutations to non-carrier family members. Furthermore, these expression levels were disease-duration dependent: the most significant decreased expression occurred after the first two years of onset, and remained steady after 6 years. These results further support the involvement of B cell-related genes in PD and correlate the level of reduced expression to disease duration.

Original languageEnglish
Pages (from-to)179-185
Number of pages7
JournalMolecular Genetics and Metabolism
Issue number2
StatePublished - 1 Feb 2016


FundersFunder number
Wolfson Foundations, Israel
Ministry of Health, State of Israel3-4893


    • Ashkenazi Jewish
    • B cells
    • Gene expression
    • Glucosidase beta acid (GBA)
    • Parkinson's disease (PD)
    • Peripheral blood leukocytes


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