Progranulin gene variability increases the risk for primary progressive multiple sclerosis in males.
Progranulin (GRN) gene variability has been analyzed in a sample of 354 patients with multiple sclerosis (MS) compared with 343 controls. No significant differences were observed, but by stratifying according to MS subtypes, a significant increased frequency of the rs2879096 TT genotype was found in primary progressive MS (PPMS) patients versus controls (16.0 vs 3.5%, P=0.023, odds ratio (OR) 5.2, 95% confidence interval (CI) 1.2-21.4). In addition, in PPMS, an association with the C allele of rs4792938 was observed (55.3 vs 33.5%, P=0.011, OR 2.4, 95% CI 1.2-4.7). An independent population was studied as replication, failing to confirm results previously obtained. Stratifying according to gender, an association with rs4792938 C allele was found in male PPMS patients compared with controls (40.7 vs 26.9%, P=0.002, OR 1.87, 95% CI 1.2-2.8). An association with the rs2879096T allele was observed (29.2 in patients compared with 18.9% in controls, P=0.012, OR 1.77, 95% CI 1.1-2.8). Haplotype analysis showed that TC haplotype frequency is increased in PPMS male patients compared with male controls (25.7 vs 16.6%; P=0.02, OR 1.69, 95% CI 1.1-2.7), whereas the respective GC haplotype seems to exert a protective effect, as its frequency is decreased in patients compared with controls (55.8% vs 70.9%; P=0.001, OR 0.52, 95% CI 0.4-0.8). Therefore, GRN haplotypes likely influence the risk of developing PPMS in males.
Fenoglio
C
C
Department of Neurological Sciences, 'Dino Ferrari' Center, University of Milan, Fondazione Ca' Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy. chiara.fenoglio@unimi.it
Scalabrini
D
D
Esposito
F
F
Comi
C
C
Cavalla
P
P
De Riz
M
M
Martinelli
V
V
Piccio
L M
LM
Venturelli
E
E
Fumagalli
G
G
Capra
R
R
Collimedaglia
L
L
Ghezzi
A
A
Rodegher
M E
ME
Vercellino
M
M
Leone
M
M
Giordana
M T
MT
Bresolin
N
N
Monaco
F
F
Comi
G
G
Scarpini
E
E
Martinelli-Boneschi
F
F
Galimberti
D
D
D000328:Adult; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D000077153:Progranulins; D012307:Risk Factors
C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins
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