Importance of SPP1 genotype as a covariate in clinical trials in Duchenne muscular dystrophy

被引：67

作者：

Bello, Luca ^{[1
]}

Piva, Luisa ^{[1
]}

Barp, Andrea ^{[1
,7
]}

Taglia, Antonella ^{[2
]}

Picillo, Esther ^{[2
]}

Vasco, Gessica ^{[3
]}

Pane, Marika ^{[3
,6
]}

Previtali, Stefano C. ^{[4
,5
]}

Torrente, Yvan ^{[6
]}

Gazzerro, Elisabetta ^{[8
]}

Motta, Maria Chiara ^{[7
]}

Grieco, Gaetano S. ^{[9
]}

Napolitano, Sara ^{[4
,5
]}

Magri, Francesca

D'Amico, Adele ^{[10
]}

Astrea, Guja ^{[11
]}

Messina, Sonia ^{[12
]}

Sframeli, Maria ^{[12
]}

Vita, Gian Luca ^{[12
]}

Boffi, Patrizia ^{[13
]}

Mongini, Tiziana ^{[13
]}

Ferlini, Alessandra ^{[14
]}

Gualandi, Francesca ^{[14
]}

Soraru', Gianni ^{[1
]}

Ermani, Mario ^{[1
]}

Vita, Giuseppe ^{[12
]}

Battini, Roberta ^{[11
]}

Bertini, Enrico ^{[10
]}

Comi, Giacomo P. ^{[6
]}

Berardinelli, Angela

Minetti, Carlo ^{[8
]}

Bruno, Claudio ^{[8
]}

Mercuri, Eugenio ^{[3
]}

Politano, Luisa ^{[2
]}

Angelini, Corrado ^{[1
]}

Hoffman, Eric P. ^{[15
]}

Pegoraro, Elena ^{[1
]}

机构：

[1] Univ Padua, Dept Neurosci, Neuromuscular Ctr, Padua, Italy

[2] Second Univ Napoli, Dept Expt Med Cardiomyol & Med Genet, Naples, Italy

[3] Catholic Univ, Dept Paediat Neurol, Rome, Italy

[4] Ist Sci San Raffaele, Dept Neurol, I-20132 Milan, Italy

[5] Ist Sci San Raffaele, INSPE, I-20132 Milan, Italy

[6] Univ Milan, Osped Maggiore Policlin, Dino Ferrari Ctr, Dept Neurol Sci,IRCCS Fdn Ca Granda, Milan, Italy

[7] Univ Pavia, Child Neurol & Psychiat Unit, IRCCS C Mondino Fdn, I-27100 Pavia, Italy

[8] G Gaslini Inst Children, Neuromuscular Dis Unit, Genoa, Italy

[9] Natl Neurol Inst C Mondino, IRCCS, Lab Expt Neurobiol, Pavia, Italy

[10] Bambino Gesu Pediat Hosp, Mol Med Unit, Dept Lab Med, Rome, Italy

[11] Univ Pisa, Dept Dev Neurosci, Stella Maris Inst, Pisa, Italy

[12] Univ Messina, Dept Neurosci Psychiat & Anaesthesiol, Messina, Italy

[13] Univ Turin, Neuromuscular Ctr, SG Battista Hosp, Turin, Italy

[14] Univ Ferrara, Dept Expt & Diagnost Med, I-44100 Ferrara, Italy

[15] Childrens Natl Med Ctr, Med Genet Res Ctr, Washington, DC 20010 USA

来源：

NEUROLOGY | 2012年 / 79卷 / 02期

关键词：

6-MINUTE WALK TEST; OSTEOPONTIN; MUSCLE;

D O I：

10.1212/WNL.0b013e31825f04ea

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

100204 [神经病学];

摘要：

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. Neurology (R) 2012;79:159-162

引用

页码：159 / 162

页数：4

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