Skip to main content
Journal cover image

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

Publication ,  Journal Article
Mastaglia, FL; Rojana-udomsart, A; James, I; Needham, M; Day, TJ; Kiers, L; Corbett, JA; Saunders, AM; Lutz, MW; Roses, AD ...
Published in: Neuromuscul Disord
December 2013

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.

Duke Scholars

Published In

Neuromuscul Disord

DOI

EISSN

1873-2364

Publication Date

December 2013

Volume

23

Issue

12

Start / End Page

969 / 974

Location

England

Related Subject Headings

  • Trinucleotide Repeat Expansion
  • Polymorphism, Single Nucleotide
  • Neurology & Neurosurgery
  • Myositis, Inclusion Body
  • Mitochondrial Precursor Protein Import Complex Proteins
  • Middle Aged
  • Membrane Transport Proteins
  • Male
  • Kaplan-Meier Estimate
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Mastaglia, F. L., Rojana-udomsart, A., James, I., Needham, M., Day, T. J., Kiers, L., … Alzheimer’s Disease Neuroimaging Initiative. (2013). Polymorphism in the TOMM40 gene modifies the risk of developing sporadic inclusion body myositis and the age of onset of symptoms. Neuromuscul Disord, 23(12), 969–974. https://doi.org/10.1016/j.nmd.2013.09.008
Mastaglia, F. L., A. Rojana-udomsart, I. James, M. Needham, T. J. Day, L. Kiers, J. A. Corbett, et al. “Polymorphism in the TOMM40 gene modifies the risk of developing sporadic inclusion body myositis and the age of onset of symptoms.Neuromuscul Disord 23, no. 12 (December 2013): 969–74. https://doi.org/10.1016/j.nmd.2013.09.008.
Mastaglia FL, Rojana-udomsart A, James I, Needham M, Day TJ, Kiers L, et al. Polymorphism in the TOMM40 gene modifies the risk of developing sporadic inclusion body myositis and the age of onset of symptoms. Neuromuscul Disord. 2013 Dec;23(12):969–74.
Mastaglia, F. L., et al. “Polymorphism in the TOMM40 gene modifies the risk of developing sporadic inclusion body myositis and the age of onset of symptoms.Neuromuscul Disord, vol. 23, no. 12, Dec. 2013, pp. 969–74. Pubmed, doi:10.1016/j.nmd.2013.09.008.
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. Polymorphism in the TOMM40 gene modifies the risk of developing sporadic inclusion body myositis and the age of onset of symptoms. Neuromuscul Disord. 2013 Dec;23(12):969–974.
Journal cover image

Published In

Neuromuscul Disord

DOI

EISSN

1873-2364

Publication Date

December 2013

Volume

23

Issue

12

Start / End Page

969 / 974

Location

England

Related Subject Headings

  • Trinucleotide Repeat Expansion
  • Polymorphism, Single Nucleotide
  • Neurology & Neurosurgery
  • Myositis, Inclusion Body
  • Mitochondrial Precursor Protein Import Complex Proteins
  • Middle Aged
  • Membrane Transport Proteins
  • Male
  • Kaplan-Meier Estimate
  • Humans