rs5848 polymorphism and serum progranulin level

Hsiung, Ging-Yuek Robin; Fok, Alice; Feldman, Howard; Rademakers, Rosa

doi:10.1016/j.jns.2010.10.009

Cited by 76 publications

(59 citation statements)

References 27 publications

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“…17,18,[33][34][35][36] It has also been speculated that rs5848 in the 3 0 UTR of GRN is a binding site for the micro-RNA miR-659 and may regulate the translation of the GRN mRNA. 37,38 Investigating these three modifying genes in our patient cohort did not reveal any association with age at onset or GRN levels in GRN-mutation carriers or the complete cohort. However, this could be due to the limited number of subjects investigated.…”

Section: Histology and Immunohistochemistrymentioning

confidence: 54%

Novel progranulin mutations with reduced serum-progranulin levels in frontotemporal lobar degeneration

et al. 2013

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Section: Histology and Immunohistochemistrymentioning

confidence: 54%

Novel progranulin mutations with reduced serum-progranulin levels in frontotemporal lobar degeneration

et al. 2013

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“…Our data support this hypothesis. The small subset of patients with the rs5848 (T:T) haplotype had significantly lower progranulin levels and were also more likely to have AD, as expected 7, 9. However, AD patients in general had higher progranulin levels, especially when excluding haplotypes that directly lower progranulin expression and cause disease.…”

Section: Discussionmentioning

confidence: 66%

“…In the CNS, progranulin expression increases with age in both neurons and microglia, and plays a role in neurite outgrowth, synapse modification, and the prevention of neuronal apoptosis 1, 2, 3, 4. This neuroprotective function is highlighted by the relationship between progranulin and neurodegenerative disease; heterozygous loss‐of‐function mutations in the gene encoding progranulin ( GRN ) cause frontotemporal dementia (FTD),5, 6 and a common rs5848 allele in the 3′UTR of GRN has been associated with both decreased serum and brain progranulin expression levels and increased risk of developing Alzheimer's disease (AD) 7, 8, 9. Additionally, misregulation of progranulin expression has been implicated in parkinsonism, neuronal ceroid lipofuscinosis, and other neuropsychiatric disorders 10, 11…”

Section: Introductionmentioning

confidence: 99%

Progranulin levels in blood in Alzheimer's disease and mild cognitive impairment

Cooper

Nachun

Dokuru

et al. 2018

Ann Clin Transl Neurol

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ObjectiveChanges in progranulin (GRN) expression have been hypothesized to alter risk for Alzheimer's disease (AD). We investigated the relationship between GRN expression in peripheral blood and clinical diagnosis of AD and mild cognitive impairment (MCI).MethodsPeripheral blood progranulin gene expression was measured, using microarrays from Alzheimer's (n = 186), MCI (n = 118), and control (n = 204) subjects from the University of California San Francisco Memory and Aging Center (UCSF‐MAC) and two independent published series (AddNeuroMed and ADNI). GRN gene expression was correlated with clinical, demographic, and genetic data, including APOE haplotype and the GRN rs5848 single‐nucleotide polymorphism. Finally, we assessed progranulin protein levels, using enzyme‐linked immunosorbent assay, and methylation status using methylation microarrays.ResultsWe observed an increase in blood progranulin gene expression and a decrease in GRN promoter methylation in males (P = 0.007). Progranulin expression was 13% higher in AD and MCI patients compared with controls in the UCSF‐MAC cohort (F 2,505 = 10.41, P = 3.72*10−5). This finding was replicated in the AddNeuroMed (F 2,271 = 17.9, P = 4.83*10−8) but not the ADNI series. The rs5848 SNP (T‐allele) predicted decreased blood progranulin gene expression (P = 0.03). The APOE4 haplotype was positively associated with progranulin expression independent of diagnosis (P = 0.04). Finally, we did not identify differences in plasma progranulin protein levels or gene methylation between diagnostic categories.InterpretationProgranulin mRNA is elevated in peripheral blood of patients with AD and MCI and its expression is associated with numerous genetic and demographic factors. These data suggest a role in the pathogenesis of neurodegenerative dementias besides frontotemporal dementia.

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“…Blood and CSF PGRN levels were correlating with each other in these studies to a minor extent [15,31]. Inter-individual differences in serum PGRN concentrations are strongly determined by the rs5848 polymorphism related to FTD risk [32,33], which could have influenced group estimates of PGRN concentrations in studies that did not check for this genetic predisposition. Since we used pools for our stability experiments, our results should not be influenced by these differences, but the effects of age, gender, or genetics might explain some of the variation found between other cohorts measured with the same commercial assay.…”

Section: Discussionmentioning

confidence: 80%

Stability of Progranulin Under Pre-Analytical Conditions in Serum and Cerebrospinal Fluid

Willemse

Durieux-Lu

Flier

et al. 2016

JAD

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Abstract. Progranulin (PGRN) levels in blood and cerebrospinal fluid (CSF) are increasingly studied as potential markers for neurodegenerative disorders. We aimed to 1) characterize two commercially available PGRN ELISAs on several assay validation parameters, 2) assess the stability of PGRN in serum and CSF under pre-analytical conditions, and 3) compare stability in the two assays. Intra-and inter-assay variation, inter-lot variation, linearity, lower limit of detection, and kit correlations were assessed for the Adipogen and R&D PGRN ELISA kits. Blood and serum samples were experimentally exposed to ≤9 freeze/thaw cycles, delayed processing for ≤24 h at room temperature and 4• C, and to temperature stability tests for ≤3 weeks at -20• C, 4• C, room temperature, and 37 • C. Both commercial PGRN ELISA kits showed acceptable ranges for intra-and inter-assay variation, where the R&D kit performed more accurate than the Adipogen kit, especially for inter-assay variation (intra-assay serum: 6.7 and 8.3%, respectively; inter-assay serum: 9.2 and 21.0%; intra-assay CSF: 3.6 and 12.0%; inter-assay CSF: 16.0 and 44.5%). Absolute serum PGRN concentrations were 1.9-fold higher in Adipogen than R&D (p < 0.001) and strongly correlated between both kits (ρ = 0.86, p < 0.0001) and CSF PGRN levels were on the borderline of detection in both kits. PGRN was typically stable under all pre-analytical conditions addressed, although two weeks at 37• C resulted in decreased PGRN concentrations in CSF, only when using the Adipogen kit. These results support further examination of PGRN as a potential marker in neurodegenerative diseases, since PGRN is stable in serum and CSF and can be measured using ELISA kits from several providers.

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rs5848 polymorphism and serum progranulin level

Cited by 76 publications

References 27 publications

Novel progranulin mutations with reduced serum-progranulin levels in frontotemporal lobar degeneration

Novel progranulin mutations with reduced serum-progranulin levels in frontotemporal lobar degeneration

Progranulin levels in blood in Alzheimer's disease and mild cognitive impairment

Stability of Progranulin Under Pre-Analytical Conditions in Serum and Cerebrospinal Fluid

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