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.

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

Cerami, Chiara;Cappa, Stefano F;
2013

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.
Adult
DNA Mutational Analysis
Female
Frontotemporal Lobar Degeneration
Humans
Intercellular Signaling Peptides and Proteins
Male
Methylation
Middle Aged
Mutation
Progranulins
Promoter Regions, Genetic
RNA, Messenger
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.12076/7659
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact