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

Mastaglia, F.L., Rojana-udomsart, A., James, I., Needham, M., Day, T.J., Kiers, L., Corbett, J.A., Saunders, A.M., Lutz, M.W. and Roses, A.D. (2013) Polymorphism in the TOMM40 gene modifies the risk of developing sporadic inclusion body myositis and the age of onset of symptoms. Neuromuscular Disorders, 23 (12). pp. 969-974.

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Link to Published Version: http://dx.doi.org/10.1016/j.nmd.2013.09.008
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Abstract

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.

Publication Type: Journal Article
Murdoch Affiliation: Institute for Immunology and Infectious Diseases
Publisher: Elsevier BV
Copyright: 2013 Elsevier B.V.
URI: http://researchrepository.murdoch.edu.au/id/eprint/18619
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