Moreover the model opens the possibility for understanding the functional differences related to the titin isoform of various muscle types and the mechanism by which mutations in titin gene lead to myopathies.
Pathogenic mutations in the gene encoding the giant skeletal muscle protein titin (TTN) are associated with several muscle disorders, including cardiomyopathy, recessive congenital myopathies and limb-girdle muscular dystrophy (LGMD) type10.
The promotion on hepatic uptake of statins mediated by OATP1B1 might lead to enhanced efficacy of cholesterol lowering and reduced risk of myopathy for hyperlipidemia patients when given statins together with deoxyschizandrin or schizandrin B.
Myopathies and muscular dystrophies (M-MDs) are genetically heterogeneous diseases, with >100 identified genes, including the giant and complex titin (TTN) and nebulin (NEB) genes.
Titin is associated with myocardial stiffness and hypertrophy, and mutations in its gene have been identified in cardiac myopathies such as dilated cardiomyopathy (DC).
The inclusion criteria were cross-sectional studies that reported the prevalence of TMD for men and women and that used the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) Axis I group diagnostic criteria:(group I = muscle disorders; group II = disc displacements; group III = arthralgias/arthritis/arthrosis).To be eligible for inclusion, studies must include adult individuals (>18 years) from a non-clinical population (ie without pre-diagnosis of TMD); in other words, from population-based studies.
So far, only 127 mutations of Titin(TTN) have been reported in patients with different phenotypes such as isolated cardiomyopathies, purely skeletal muscle phenotypes or complex overlapping disorders of muscles.
The findings of this study indicated that SLCO1B1T521C was associated with a significantly higher risk of statin-induced myopathy, especially for simvastatin, rosuvastatin, and cerivastatin.
Many studies have focused on the consequences of OATP1B1 variants to statin disposition in vitro and in vivo and would suggest that genetic variability in SLCO1B1 has important implications for statin pharmacokinetics, risk for statin-induced myopathy, and modulation of statin treatment response.
Homozygous truncating mutation in prenatally expressed skeletal isoform of TTN gene results in arthrogryposis multiplex congenita and myopathy without cardiac involvement.
Electron microscopy revealed extensive ultrastructural changes in myofibers of various hereditary myopathies and also suggested massive binding of proteins to the sarcomeric I-band region, presumably heat shock proteins (HSPs), which can translocate to elastic titin under stress conditions.