title: Importance of SPP1 genotype as a covariate in clinical trials in Duchenne muscular dystrophy.
abstract: 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.
authors: Neuromuscular Center, Department of Neurosciences, University of Padova, Padova.
authors: Luca
authors: L
authors: Bello
authors: Luisa
authors: L
authors: Piva
authors: Andrea
authors: A
authors: Barp
authors: Antonella
authors: A
authors: Taglia
authors: Esther
authors: E
authors: Picillo
authors: Gessica
authors: G
authors: Vasco
authors: Marika
authors: M
authors: Pane
authors: Stefano C
authors: SC
authors: Previtali
authors: Yvan
authors: Y
authors: Torrente
authors: Elisabetta
authors: E
authors: Gazzerro
authors: Maria Chiara
authors: MC
authors: Motta
authors: Gaetano S
authors: GS
authors: Grieco
authors: Sara
authors: S
authors: Napolitano
authors: Francesca
authors: F
authors: Magri
authors: Adele
authors: A
authors: D'Amico
authors: Guja
authors: G
authors: Astrea
authors: Sonia
authors: S
authors: Messina
authors: Maria
authors: M
authors: Sframeli
authors: Gian Luca
authors: GL
authors: Vita
authors: Patrizia
authors: P
authors: Boffi
authors: Tiziana
authors: T
authors: Mongini
authors: Alessandra
authors: A
authors: Ferlini
authors: Francesca
authors: F
authors: Gualandi
authors: Gianni
authors: G
authors: Soraru'
authors: Mario
authors: M
authors: Ermani
authors: Giuseppe
authors: G
authors: Vita
authors: Roberta
authors: R
authors: Battini
authors: Enrico
authors: E
authors: Bertini
authors: Giacomo P
authors: GP
authors: Comi
authors: Angela
authors: A
authors: Berardinelli
authors: Carlo
authors: C
authors: Minetti
authors: Claudio
authors: C
authors: Bruno
authors: Eugenio
authors: E
authors: Mercuri
authors: Luisa
authors: L
authors: Politano
authors: Corrado
authors: C
authors: Angelini
authors: Eric P
authors: EP
authors: Hoffman
authors: Elena
authors: E
authors: Pegoraro
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D008137:Longitudinal Studies; D015337:Multicenter Studies as Topic; D020388:Muscular Dystrophy, Duchenne / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D053495:Osteopontin / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: C506895:SPP1 protein, human; D053495:Osteopontin