RESUMO
Facioscapulohumeral muscular dystrophy (FSHD) is a progressive muscle disorder that has been associated with a contraction of 3.3-kb repeats on chromosome 4q35. FSHD is characterized by a wide clinical inter- and intrafamilial variability, ranging from wheelchair-bound patients to asymptomatic carriers. Our study is unique in comparing the gene expression profiles from related affected, asymptomatic carrier, and control individuals. Our results suggest that the expression of genes on chromosome 4q is altered in affected and asymptomatic individuals. Remarkably, the changes seen in asymptomatic samples are largely in products of genes encoding several chemokines, whereas the changes seen in affected samples are largely in genes governing the synthesis of GPI-linked proteins and histone acetylation. Besides this, the affected patient and related asymptomatic carrier share the 4qA161 haplotype. Thus, these polymorphisms by themselves do not explain the pathogenicity of the contracted allele. Interestingly, our results also suggest that the miRNAs might mediate the regulatory network in FSHD. Together, our results support the previous evidence that FSHD may be caused by transcriptional dysregulation of multiple genes, in cis and in trans, and suggest some factors potentially important for FSHD pathogenesis. The study of the gene expression profiles from asymptomatic carriers and related affected patients is a unique approach to try to enhance our understanding of the missing link between the contraction in D4Z4 repeats and muscle disease, while minimizing the effects of differences resulting from genetic background.
Assuntos
Regulação da Expressão Gênica/genética , Heterozigoto , Distrofia Muscular Facioescapuloumeral/genética , Transcrição Gênica/genética , Estudos de Casos e Controles , Cromossomos Humanos Par 4/genética , Perfilação da Expressão Gênica , Humanos , Polimorfismo Genético/genéticaRESUMO
Long-distance runners generally have a remarkably high proportion of slow type I fibers in their lower muscle groups. However, the transformation of type II fast fibers to slow type I fibers as a result of exercise has not been demonstrated clearly. We report the analysis of muscle type composition on m. vastus lateralis from six endurance athletes through the expression of fast, slow, and developmental myosin isoforms, and alpha-actinin-3 (ACTN3) protein. Only one among the marathon runners presented evident type I fiber predominance, and surprisingly, a second athlete showed a deficiency of ACTN3. The deficiency of ACTN3 in the muscle tissue of endurance athletes confirmed the redundancy of this protein for muscle function, even in muscles that are highly required.