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

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.

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Acknowledgements

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.

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Correspondence to C Fenoglio.

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Fenoglio, C., Scalabrini, D., Esposito, F. et al. Progranulin gene variability increases the risk for primary progressive multiple sclerosis in males. Genes Immun 11, 497–503 (2010). https://doi.org/10.1038/gene.2010.18

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