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Progranulin gene (GRN) promoter methylation is increased in patients with sporadic frontotemporal lobar degeneration

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Abstract

Mutations in progranulin gene (GRN) are the most common cause of autosomal dominant familial frontotemporal lobar degeneration (FTLD). In addition, GRN variability influences the risk to develop the disease in non-carriers (sporadic FTLD). We evaluated progranulin gene (GRN) promoter methylation levels in peripheral blood mononuclear cells isolated from 38 patients with sporadic FTLD compared with 38 controls, and correlate them with GRN mRNA expression rate. The percentage of methylation of the GRN promoter was increased in patients with FTLD compared with controls (61.5 vs. 46.3 %, P < 0.001). A trend towards decreased GRN relative expression was observed in patients compared with controls (threefold decrease over controls, P > 0.05), together with a negative correlation between the degree of GRN promoter methylation and mRNA GRN levels (ρ = −0.1, P > 0.05). GRN promoter methylation was not correlated with age. In conclusion, the degree of methylation of the GRN promoter is increased in patients with FTLD as compared with controls, likely leading to a decreased expression of GRN.

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Acknowledgments

This work was supported by grants from Italian Ministry of Health (Ricerca Corrente and additional fund 5x1000 2008), Monzino Foundation and TERCAS (2009–2012) to MM.

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Authors and Affiliations

  1. Department of Biomedical Sciences, University of Teramo, Teramo, Italy

    Claudio D’Addario & Mauro Maccarrone

  2. Department of Medical Sciences and Community Health, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy

    Beatrice Arosio & Daniela Mari

  3. Department of Neurology, Scientific Institute S. Raffaele, Vita-Salute University, Milan, Italy

    Alessandra Marcone, Chiara Cerami & Stefano F. Cappa

  4. Department of Pathophysiology and Transplantation, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy

    Daniela Galimberti, Bernardo Dell’Osso, Chiara Fenoglio, M. Carlotta Palazzo, Nereo Bresolin, A. Carlo Altamura & Elio Scarpini

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  1. Daniela Galimberti
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  2. Claudio D’Addario
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Correspondence to Daniela Galimberti.

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Galimberti, D., D’Addario, C., Dell’Osso, B. et al. Progranulin gene (GRN) promoter methylation is increased in patients with sporadic frontotemporal lobar degeneration. Neurol Sci 34, 899–903 (2013). https://doi.org/10.1007/s10072-012-1151-5

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  • DOI: https://doi.org/10.1007/s10072-012-1151-5

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