Genótipo SPP1 é determinante para a severidade da distrofia muscular de Duchenne

USA - pacientes com distrofia muscular de Duchenne podem apresentar a doença com sintomas mais severos ou brandos, mais precoces ou mais tardios. Os pesquisadores procuram marcadores para identificar estes grupos de doentes. Estudando uma população grande de pacientes com Duchenne e separados de acordo com doença leve ou severa identificaram que a mutação do gene SPP1 da osteopontina é que pode determinar a variabilidade da evolução da doença. Seria possível modificar a expressão deste gene para melhorar a evolução da doença? Não há respostas até o momento.

O resumo em inglês pode ser lido abaixo:

(Neurology,2011) SPP1 genotype is a determinant of disease severity in Duchenne muscular dystrophy

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, and On behalf of the Cooperative International Neuromuscular Research Group

Objective: Duchenne muscular dystrophy (DMD) is the most common single-gene lethal disorder. Substantial patient–patient variability in disease onset and progression and response to glucocorticoids is seen, suggesting genetic or environmental modifiers

Methods: Two DMD cohorts were used as test and validation groups to define genetic modifiers: a Padova longitudinal cohort (n = 106) and the Cooperative International Neuromuscular Research Group (CINRG) cross-sectional natural history cohort (n = 156). Single nucleotide polymorphisms to be genotyped were selected from mRNA profiling in patients with severe vs mild DMD, and genome-wide association studies in metabolism and polymorphisms influencing muscle phenotypes in normal volunteers were studied

Results: Effects on both disease progression and response to glucocorticoids were observed with polymorphism rs28357094 in the gene promoter of SPP1 (osteopontin). The G allele (dominant model; 35% of subjects) was associated with more rapid progression (Padova cohort log rank p = 0.003), and 12%–19% less grip strength (CINRG cohort p = 0.0003).

Conclusions: Osteopontin genotype is a genetic modifier of disease severity in Duchenne dystrophy. Inclusion of genotype data as a covariate or in inclusion criteria in DMD clinical trials would reduce intersubject variance, and increase sensitivity of the trials, particularly in older subjects.

Fonte: http://distrofiamuscular.net/noticias.htm