SPP1 genotype is a determinant of disease severity in Duchenne muscular dystrophy

• DOI: 10.1212/wnl.0b013e318207afeb
• Publication Date: 2010-12-23T04:02:19Z
• Authors: E. Pegoraro; E.P. Hoffman; L. Piva; B.F. Gavassini; S. Cagnin; M. Ermani; L. Bello; G. Soraru; B. Pacchioni; M.D. Bonifati; G. Lanfranchi; C. Angelini; A. Kesari; I. Lee; H. Gordish-Dressman; J.M. Devaney; C.M. McDonald
• Keywords: Neuromuscular disease

Duchenne muscular dystrophy (DMD) is the most common single-gene lethal disorder. Substantial patient-patient variability in disease onset and progression response to glucocorticoids seen, suggesting genetic or environmental modifiers.Two DMD cohorts were used as test validation groups define modifiers: a Padova longitudinal cohort (n = 106) Cooperative International Neuromuscular Research Group (CINRG) cross-sectional natural history 156). Single nucleotide polymorphisms be genotyped selected from mRNA profiling patients with severe vs mild DMD, genome-wide association studies metabolism influencing muscle phenotypes normal volunteers studied.Effects on both observed polymorphism rs28357094 gene promoter of SPP1 (osteopontin). The G allele (dominant model; 35% subjects) was associated more rapid (Padova log rank p 0.003), 12%-19% less grip strength (CINRG 0.0003).Osteopontin genotype modifier severity dystrophy. Inclusion data covariate inclusion criteria clinical trials would reduce intersubject variance, increase sensitivity trials, particularly older subjects.