TY - JOUR
T1 - Progranulin gene variability increases the risk for primary progressive multiple sclerosis in males
AU - FENOGLIO, C
AU - SCALABRINI, D
AU - ESPOSITO, F
AU - COMI, Cristoforo
AU - CAVALLA, P
AU - DE, RIZ M
AU - MARTINELLI, V
AU - LM, PICCIO
AU - VENTURELLI, E
AU - FUMAGALLI, G
AU - CAPRA, R
AU - COLLIMEDAGLIA, L
AU - GHEZZI, A
AU - ME, RODEGHER
AU - VERCELLINO, M
AU - LEONE, M
AU - MT, GIORDANA
AU - BRESOLIN, N
AU - MONACO, Francesco
AU - COMI, G
AU - SCARPINI, E
AU - MARTINELLI, BONESCHI F
AU - GALIMBERTI, D.
N1 - Funding Information:
This work was supported by grants from Bayer, IRCCS Ospedale Maggiore Policlinico (Milano) to DG and CC, Italian Ministry of Health to FMB (Giovani Ricercatori 2007, D.lgs 502/92), Monzino Foundation, Ing. Cesare Cusan and Regione Piemonte, Ricerca Sanitaria Finalizzata 2007.
PY - 2010
Y1 - 2010
N2 - 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%, P0.023, 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%, P0.011, 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%, P0.002, 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, P0.012, 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%; P0.02, 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%; P0.001, OR 0.52, 95% CI 0.4-0.8). Therefore, GRN haplotypes likely influence the risk of developing PPMS in males.
AB - 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%, P0.023, 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%, P0.011, 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%, P0.002, 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, P0.012, 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%; P0.02, 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%; P0.001, OR 0.52, 95% CI 0.4-0.8). Therefore, GRN haplotypes likely influence the risk of developing PPMS in males.
UR - https://iris.uniupo.it/handle/11579/23787
U2 - 10.1038/gene.2010.18
DO - 10.1038/gene.2010.18
M3 - Article
SN - 1466-4879
VL - 11
SP - 497
EP - 503
JO - Genes and Immunity
JF - Genes and Immunity
IS - 6
ER -