학술논문
Progranulin gene variability increases the risk for primary progressive multiple sclerosis in males
Document Type
Academic Journal
Author
Fenoglio, C; Scalabrini, D; Esposito, F; Comi, C; Cavalla, P; De Riz, M; Martinelli, V; Piccio, L M; Venturelli, E; Fumagalli, G; Capra, R; Collimedaglia, L; Ghezzi, A; Rodegher, M E; Vercellino, M; Leone, M; Giordana, M T; Bresolin, N; Monaco, F; Comi, G; Scarpini, E; Martinelli-Boneschi, F; Galimberti, D
Source
Genes and Immunity. Sep 01, 2010 11(6):497-503
Subject
Language
English
ISSN
1466-4879
Abstract
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.