The effects of an intronic polymorphism in TOMM40 and APOE genotypes in sporadic inclusion body myositis

Qiang Gang, Conceicao Bettencourt, Pedro M. Machado, Zoe Fox, Stefen Brady, Estelle Healy, Matt Parton, Janice L. Holton, David Hilton-Jones, Perry B. Shieh, Edmar Zanoteli, Boel De Paepe, Jan De Bleecker, Aziz Shaibani, Michela Ripolone, Raffaella Violano, Maurizio Moggio, Richard J. Barohn, Mazen M. Dimachkie, Marina MoraRenato Mantegazza, Simona Zanotti, Michael G. Hanna, Henry Houlden

Research output: Contribution to journalArticlepeer-review


A previous study showed that, in carriers of the apolipoprotein E (. APOE) genotype ε3/ε3 or ε3/ε4, the presence of a very long (VL) polyT repeat allele in "translocase of outer mitochondrial membrane 40" (. TOMM40) was less frequent in patients with sporadic inclusion body myositis (sIBM) compared with controls and associated with a later age of sIBM symptom onset, suggesting a protective effect of this haplotype. To further investigate the influence of these genetic factors in sIBM, we analyzed a large sIBM cohort of 158 cases as part of an International sIBM Genetics Study. No significant association was found between APOE or TOMM40 genotypes and the risk of developing sIBM. We found that the presence of at least 1 VL polyT repeat allele in TOMM40 was significantly associated with about 4 years later onset of sIBM symptoms. The age of onset was delayed by 5 years when the patients were also carriers of the APOE genotype ε3/ε3. In addition, males were likely to have a later age of onset than females. Therefore, the TOMM40 VL polyT repeat, although not influencing disease susceptibility, has a disease-modifying effect on sIBM, which can be enhanced by the APOE genotype ε3/ε3.

Original languageEnglish
Pages (from-to)1766.e1-1766.e3
JournalNeurobiology of Aging
Issue number4
Publication statusPublished - Apr 1 2015


  • Age of onset
  • APOE
  • SIBM
  • Sporadic inclusion body myositis
  • TOMM40

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Ageing
  • Developmental Biology
  • Geriatrics and Gerontology


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