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

Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
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