Importance of SPP1 genotype as a covariate in clinical trials in Duchenne muscular dystrophy.
Neurology
; 79(2): 159-62, 2012 Jul 10.
Article
en En
| MEDLINE
| ID: mdl-22744661
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Distrofia Muscular de Duchenne
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Polimorfismo de Nucleótido Simple
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Osteopontina
Tipo de estudio:
Diagnostic_studies
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Observational_studies
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Prognostic_studies
Límite:
Adolescent
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Adult
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Child
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Child, preschool
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Humans
Idioma:
En
Revista:
Neurology
Año:
2012
Tipo del documento:
Article