Progranulin gene variability increases the risk for primary progressive multiple sclerosis in males

C. Fenoglio, D. Scalabrini, F. Esposito, C. Comi, P. Cavalla, M. De Riz, V. Martinelli, L. M. Piccio, E. Venturelli, G. Fumagalli, R. Capra, L. Collimedaglia, A. Ghezzi, M. E. Rodegher, M. Vercellino, M. Leone, M. T. Giordana, N. Bresolin, F. Monaco, G. ComiE. Scarpini, F. Martinelli-Boneschi, D. Galimberti

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13 Scopus citations


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.

Original languageEnglish
Pages (from-to)497-503
Number of pages7
JournalGenes and Immunity
Issue number6
StatePublished - Sep 2010


  • gender
  • neurodegeneration
  • primary progressive multiple sclerosis
  • progranulin
  • risk factor
  • single-nucleotide polymorphism


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