Polymorphism in the TOMM40 gene modifies the risk of developing sporadic inclusion body myositis and the age of onset of symptoms.
Published
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
Pubmed Central ID
- 24103330
Electronic International Standard Serial Number (EISSN)
- 1873-2364
Digital Object Identifier (DOI)
- 10.1016/j.nmd.2013.09.008
Language
- eng
Conference Location
- England