Neurological Sciences

, Volume 34, Issue 6, pp 899–903 | Cite as

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

  • Daniela Galimberti
  • Claudio D’Addario
  • Bernardo Dell’Osso
  • Chiara Fenoglio
  • Alessandra Marcone
  • Chiara Cerami
  • Stefano F. Cappa
  • M. Carlotta Palazzo
  • Beatrice Arosio
  • Daniela Mari
  • Mauro Maccarrone
  • Nereo Bresolin
  • A. Carlo Altamura
  • Elio Scarpini
Original Article

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.

Keywords

Frontotemporal lobar degeneration (FTLD) Progranulin (GRN) Methylation Peripheral mononuclear cells (PBMC) Expression 

Notes

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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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Daniela Galimberti
    • 4
  • Claudio D’Addario
    • 1
  • Bernardo Dell’Osso
    • 4
  • Chiara Fenoglio
    • 4
  • Alessandra Marcone
    • 3
  • Chiara Cerami
    • 3
  • Stefano F. Cappa
    • 3
  • M. Carlotta Palazzo
    • 4
  • Beatrice Arosio
    • 2
  • Daniela Mari
    • 2
  • Mauro Maccarrone
    • 1
  • Nereo Bresolin
    • 4
  • A. Carlo Altamura
    • 4
  • Elio Scarpini
    • 4
  1. 1.Department of Biomedical SciencesUniversity of TeramoTeramoItaly
  2. 2.Department of Medical Sciences and Community HealthUniversity of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore PoliclinicoMilanItaly
  3. 3.Department of Neurology, Scientific Institute S. RaffaeleVita-Salute UniversityMilanItaly
  4. 4.Department of Pathophysiology and TransplantationUniversity of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore PoliclinicoMilanItaly

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