title: Down-regulation of B cell-related genes in peripheral blood leukocytes of Parkinson's disease patients with and without GBA mutations.
abstract: 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 them were 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) or without (n = 15) GBA mutations. In qRT-PCR analysis, all five genes were down-regulated in patients (PD-GBA 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.
authors.affiliation: The Genetic Institute, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel; The Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel. Electronic address: hilako@tlvmc.gov.il.
authors.forename: Hila
authors.initials: H
authors.lastname: Kobo
authors.affiliation: The Genetic Institute, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel. Electronic address: anatbn@tlvmc.gov.il.
authors.forename: Anat
authors.initials: A
authors.lastname: Bar-Shira
authors.affiliation: The Genetic Institute, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel. Electronic address: dvir.dahary@gmail.com.
authors.forename: Dvir
authors.initials: D
authors.lastname: Dahary
authors.affiliation: The Genetic Institute, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel. Electronic address: ziv.gan-or@mail.mcgill.ca.
authors.forename: Ziv
authors.initials: Z
authors.lastname: Gan-Or
authors.affiliation: Movement Disorders Unit, Parkinson Center, Department of Neurology, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel. Electronic address: anatmi@tlvmc.gov.il.
authors.forename: Anat
authors.initials: A
authors.lastname: Mirelman
authors.affiliation: The Genetic Institute, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel. Electronic address: orlyg@tlvmc.gov.il.
authors.forename: Orly
authors.initials: O
authors.lastname: Goldstein
authors.affiliation: Movement Disorders Unit, Parkinson Center, Department of Neurology, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel; The Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel. Electronic address: nirg@tlvmc.gov.il.
authors.forename: Nir
authors.initials: N
authors.lastname: Giladi
authors.affiliation: The Genetic Institute, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel; The Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel. Electronic address: aviorr@tasmc.health.gov.il.
authors.forename: Avi
authors.initials: A
authors.lastname: Orr-Urtreger
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D018941:Antigens, CD19 / Q000235:genetics / Q000378:metabolism; D051925:CD79 Antigens / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics* / Q000378:metabolism; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome; D001617:beta-Glucosidase / Q000235:genetics*
chemical_list: D015703:Antigens, CD; D018941:Antigens, CD19; C092722:CD180 protein, human; C497867:CD22 protein, human; D051925:CD79 Antigens; C551993:FCRL1 protein, human; D008565:Membrane Proteins; D051918:Sialic Acid Binding Ig-like Lectin 2; D001617:beta-Glucosidase
keywords: Ashkenazi Jewish; B cells; Gene expression; Glucosidase beta acid (GBA); Parkinson's disease (PD); Peripheral blood leukocytes