Sporadic inclusion body myositis: the genetic contributions to the pathogenesis

Abstract

Sporadic inclusion body myositis (sIBM) is the commonest idiopathic inflammatory muscle disease in people over 50 years old. It is characterized by slowly progressive muscle weakness and atrophy, with typical pathological changes of inflammation, degeneration and mitochondrial abnormality in affected muscle fibres. The cause(s) of sIBM are still unknown, but are considered complex, with the contribution of multiple factors such as environmental triggers, ageing and genetic susceptibility. This review summarizes the current understanding of the genetic contributions to sIBM and provides some insights for future research in this mysterious disease with the advantage of the rapid development of advanced genetic technology. An international sIBM genetic study is ongoing and whole-exome sequencing will be applied in a large cohort of sIBM patients with the aim of unravelling important genetic risk factors for sIBM.

Figure 1

Possible pathogenic pathways of sIBM – multifactorial mechanisms involved. An inflammation pathway and a degeneration pathway constitute the two most popular theories for the pathogenesis of sIBM. Ageing is also considered an important factor contributing to mitochondrial dysfunction in result of oxidative stress in the muscle tissue. However, it is still not clear which is the primary cause of the disease, and how these potential pathways interact. Predisposing genes could also contribute to the development and progression of the disease.