TY - JOUR
T1 - Importance of SPP1 genotype as a covariate in clinical trials in Duchenne muscular dystrophy
AU - Bello, Luca
AU - Piva, Luisa
AU - Barp, Andrea
AU - Taglia, Antonella
AU - Picillo, Esther
AU - Vasco, Gessica
AU - Pane, Marika
AU - Previtali, Stefano C.
AU - Torrente, Yvan
AU - Gazzerro, Elisabetta
AU - Motta, Maria Chiara
AU - Grieco, Gaetano S.
AU - Napolitano, Sara
AU - Magri, Francesca
AU - D'Amico, Adele
AU - Astrea, Guja
AU - Messina, Sonia
AU - Sframeli, Maria
AU - Vita, Gian Luca
AU - Boffi, Patrizia
AU - Mongini, Tiziana
AU - Ferlini, Alessandra
AU - Gualandi, Francesca
AU - Soraru, Gianni
AU - Ermani, Mario
AU - Vita, Giuseppe
AU - Battini, Roberta
AU - Bertini, Enrico
AU - Comi, Giacomo P.
AU - Berardinelli, Angela
AU - Minetti, Carlo
AU - Bruno, Claudio
AU - Mercuri, Eugenio
AU - Politano, Luisa
AU - Angelini, Corrado
AU - Hoffman, Eric P.
AU - Pegoraro, Elena
PY - 2012/7/10
Y1 - 2012/7/10
N2 - Objective: To test the effect of the single nucleotide polymorphism -66 T>G (rs28357094) in the osteopontin gene (SPP1) on functional measures over 12 months in Duchenne muscular dystrophy (DMD). Methods: This study was conducted on a cohort of ambulatory patients with DMD from a network of Italian neuromuscular centers, evaluated longitudinally with the North Star Ambulatory Assessment (NSAA) and the 6-Minute Walk Test (6MWT) at study entry and after 12 months. Genotype at rs28357094 was determined after completion of the clinical evaluations. Patients were stratified in 2 groups according to a dominant model (TT homozygotes vs TG heterozygotes and GG homozygotes) and clinical data were retrospectively compared between groups. Results: Eighty patients were selected (age 4.1-19.3 years; mean 8.3 ± 2.7 SD). There were no differences in age or steroid treatment between the 2 subgroups. Paired t test showed a significant difference in both NSAA (p = 0.013) and 6MWT (p = 0.03) between baseline and follow-up after 12 months in patients with DMD carrying the G allele. The difference was not significant in the T subgroup. The analysis of covariance using age and baseline values as covariate and SPP1 genotype as fixed effect showed that these parameters are significantly correlated with the 12-month values. Conclusions: These data provide evidence of the role of SPP1 genotype as a disease modifier in DMD and support its relevance in the selection of homogeneous groups of patients for future clinical trials.
AB - Objective: To test the effect of the single nucleotide polymorphism -66 T>G (rs28357094) in the osteopontin gene (SPP1) on functional measures over 12 months in Duchenne muscular dystrophy (DMD). Methods: This study was conducted on a cohort of ambulatory patients with DMD from a network of Italian neuromuscular centers, evaluated longitudinally with the North Star Ambulatory Assessment (NSAA) and the 6-Minute Walk Test (6MWT) at study entry and after 12 months. Genotype at rs28357094 was determined after completion of the clinical evaluations. Patients were stratified in 2 groups according to a dominant model (TT homozygotes vs TG heterozygotes and GG homozygotes) and clinical data were retrospectively compared between groups. Results: Eighty patients were selected (age 4.1-19.3 years; mean 8.3 ± 2.7 SD). There were no differences in age or steroid treatment between the 2 subgroups. Paired t test showed a significant difference in both NSAA (p = 0.013) and 6MWT (p = 0.03) between baseline and follow-up after 12 months in patients with DMD carrying the G allele. The difference was not significant in the T subgroup. The analysis of covariance using age and baseline values as covariate and SPP1 genotype as fixed effect showed that these parameters are significantly correlated with the 12-month values. Conclusions: These data provide evidence of the role of SPP1 genotype as a disease modifier in DMD and support its relevance in the selection of homogeneous groups of patients for future clinical trials.
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U2 - 10.1212/WNL.0b013e31825f04ea
DO - 10.1212/WNL.0b013e31825f04ea
M3 - Article
C2 - 22744661
AN - SCOPUS:84866252725
VL - 79
SP - 159
EP - 162
JO - Neurology
JF - Neurology
SN - 0028-3878
IS - 2
ER -