Progranulin gene (GRN) promoter methylation is increased in patients with sporadic frontotemporal lobar degeneration.
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.
Department of Pathophysiology and Transplantation, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy. daniela.galimberti@unimi.it
Daniela
D
Galimberti
Claudio
C
D'Addario
Bernardo
B
Dell'osso
Chiara
C
Fenoglio
Alessandra
A
Marcone
Chiara
C
Cerami
Stefano F
SF
Cappa
M Carlotta
MC
Palazzo
Beatrice
B
Arosio
Daniela
D
Mari
Mauro
M
Maccarrone
Nereo
N
Bresolin
A Carlo
AC
Altamura
Elio
E
Scarpini
D000328:Adult; D004252:DNA Mutational Analysis; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000097:blood / Q000235:genetics*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood / Q000235:genetics*; D008297:Male; D008745:Methylation; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D000077153:Progranulins; D011401:Promoter Regions, Genetic / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism
C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins; D012333:RNA, Messenger