Polymorphism in the TOMM40 gene modifies the risk of developing sporadic inclusion body myositis and the age of onset of symptoms.

Journal Article (Journal Article)

A polyT repeat in an intronic polymorphism (rs10524523) in the TOMM40 gene, which encodes an outer mitochondrial membrane translocase involved in the transport of amyloid-β and other proteins into mitochondria, has been implicated in Alzheimer's disease and APOE-TOMM40 genotypes have been shown to modify disease risk and age at onset of symptoms. Because of the similarities between Alzheimer's disease and sporadic inclusion body myositis (s-IBM), and the importance of amyloid-β and mitochondrial changes in s-IBM, we investigated whether variation in poly-T repeat lengths in rs10524523 also influence susceptibility and age at onset in a cohort of 90 Caucasian s-IBM patients (55 males; age 69.1 ± 9.6). In carriers of APOE ε3/ε3 or ε3/ε4, genotypes with a very long (VL) poly-T repeat were under-represented in s-IBM compared to controls and were associated with a later age at symptom onset, suggesting that these genotypes may be protective. Our study is the first to suggest that polymorphisms in genes controlling mitochondrial function can influence susceptibility to s-IBM and have disease modifying effects. However, further studies in other s-IBM populations are needed to confirm these findings, as well as expression studies of different TOMM40 alleles in muscle tissue.

Full Text

Duke Authors

Cited Authors

  • Mastaglia, FL; Rojana-udomsart, A; James, I; Needham, M; Day, TJ; Kiers, L; Corbett, JA; Saunders, AM; Lutz, MW; Roses, AD; Alzheimer’s Disease Neuroimaging Initiative,

Published Date

  • December 2013

Published In

Volume / Issue

  • 23 / 12

Start / End Page

  • 969 - 974

PubMed ID

  • 24103330

Electronic International Standard Serial Number (EISSN)

  • 1873-2364

Digital Object Identifier (DOI)

  • 10.1016/j.nmd.2013.09.008


  • eng

Conference Location

  • England