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

F.L. Mastaglia; A. Rojana-udomsart; I. James; M. Needham; T.J. Day; L. Kiers; J.A. Corbett; A.M. Saunders; M.W. Lutz; A.D. Roses

doi:10.1016/j.nmd.2013.09.008

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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

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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

F.L. Mastaglia, A. Rojana-udomsart, I. James, M. Needham, T.J. Day, L. Kiers, J.A. Corbett, A.M. Saunders, M.W. Lutz and A.D. Roses

Neuromuscular Disorders, Vol.23(12), pp.969-974

2013

DOI: https://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.

Details

Title: Polymorphism in the TOMM40 gene modifies the risk of developing sporadic inclusion body myositis and the age of onset of symptoms
Authors/Creators: F.L. Mastaglia (Author/Creator) - Murdoch University
A. Rojana-udomsart (Author/Creator) - The University of Western Australia
I. James (Author/Creator) - Murdoch University
M. Needham (Author/Creator) - Murdoch University
T.J. Day (Author/Creator) - The Royal Melbourne Hospital
L. Kiers (Author/Creator) - The Royal Melbourne Hospital
J.A. Corbett (Author/Creator) - Department of Neurology, Concord Hospital, Concord, NSW, Australia.
A.M. Saunders (Author/Creator) - Duke University
M.W. Lutz (Author/Creator) - Duke University
A.D. Roses (Author/Creator) - Duke University
Publication Details: Neuromuscular Disorders, Vol.23(12), pp.969-974
Publisher: Elsevier BV
Identifiers: 991005540075607891
Copyright: 2013 Elsevier B.V.
Murdoch Affiliation: Institute for Immunology and Infectious Diseases
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.106 Rheumatology; 1.106.1684 Dermatomyositis
Web Of Science research areas: Clinical Neurology; Neurosciences
ESI research areas: Neuroscience & Behavior