The effects of an intronic polymorphism in TOMM40 and APOE genotypes in sporadic inclusion body myositis

Q. Gang; C. Bettencourt; P.M. Machado; Z. Fox; S. Brady; E. Healy; M. Parton; J.L. Holton; D. Hilton-Jones; P.B. Shieh; E. Zanoteli; B. De Paepe; J. De Bleecker; A. Shaibani; M. Ripolone; R. Violano; M. Moggio; R.J. Barohn; M.M. Dimachkie; M. Mora; R. Mantegazza; S. Zanotti; M.G. Hanna; H. Houlden; M. Needham; F. Mastaglia

doi:10.1016/j.neurobiolaging.2014.12.039

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The effects of an intronic polymorphism in TOMM40 and APOE genotypes in sporadic inclusion body myositis

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The effects of an intronic polymorphism in TOMM40 and APOE genotypes in sporadic inclusion body myositis

Q. Gang, C. Bettencourt, P.M. Machado, Z. Fox, S. Brady, E. Healy, M. Parton, J.L. Holton, D. Hilton-Jones, P.B. Shieh, …

Neurobiology of Aging, Vol.36(4), pp.1766.e1-1766.e3

2015

DOI: https://doi.org/10.1016/j.neurobiolaging.2014.12.039

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Abstract

A previous study showed that, in carriers of the apolipoprotein E (APOE) genotype ε3/ε3 or ε3/ε4, the presence of a very long (VL) polyT repeat allele in “translocase of outer mitochondrial membrane 40” (TOMM40) was less frequent in patients with sporadic inclusion body myositis (sIBM) compared with controls and associated with a later age of sIBM symptom onset, suggesting a protective effect of this haplotype. To further investigate the influence of these genetic factors in sIBM, we analyzed a large sIBM cohort of 158 cases as part of an International sIBM Genetics Study. No significant association was found between APOE or TOMM40 genotypes and the risk of developing sIBM. We found that the presence of at least 1 VL polyT repeat allele in TOMM40 was significantly associated with about 4 years later onset of sIBM symptoms. The age of onset was delayed by 5 years when the patients were also carriers of the APOE genotype ε3/ε3. In addition, males were likely to have a later age of onset than females. Therefore, the TOMM40 VL polyT repeat, although not influencing disease susceptibility, has a disease-modifying effect on sIBM, which can be enhanced by the APOE genotype ε3/ε3.

Details

Title: The effects of an intronic polymorphism in TOMM40 and APOE genotypes in sporadic inclusion body myositis
Authors/Creators: Q. Gang (Author/Creator) - University College London
C. Bettencourt (Author/Creator) - UCL Institute of Neurology
P.M. Machado (Author/Creator) - University College London
Z. Fox (Author/Creator) - UCL Biomedical Research Centre
S. Brady (Author/Creator) - University College London
E. Healy (Author/Creator) - University College London
M. Parton (Author/Creator) - University College London
J.L. Holton (Author/Creator) - University College London
D. Hilton-Jones (Author/Creator) - University of Oxford
P.B. Shieh (Author/Creator) - University of California, Los Angeles
E. Zanoteli (Author/Creator) - Universidade de São Paulo
B. De Paepe (Author/Creator) - Ghent University Hospital
J. De Bleecker (Author/Creator) - Ghent University Hospital
A. Shaibani (Author/Creator) - Nerve and Muscle Centre of Texas, Houston, TX, USA
M. Ripolone (Author/Creator) - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
R. Violano (Author/Creator) - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
M. Moggio (Author/Creator) - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
R.J. Barohn (Author/Creator) - University of Kansas Medical Center
M.M. Dimachkie (Author/Creator) - University of Kansas Medical Center
M. Mora (Author/Creator) - Fondazione IRCCS Istituto Neurologico Carlo Besta
R. Mantegazza (Author/Creator) - Fondazione IRCCS Istituto Neurologico Carlo Besta
S. Zanotti (Author/Creator) - Fondazione IRCCS Istituto Neurologico Carlo Besta
M.G. Hanna (Author/Creator) - University College London
H. Houlden (Author/Creator) - University College London
M. Needham (Author/Creator)
F. Mastaglia (Author/Creator)
Publication Details: Neurobiology of Aging, Vol.36(4), pp.1766.e1-1766.e3
Publisher: Elsevier Inc
Identifiers: 991005543117507891
Copyright: © 2015 The Authors.
Murdoch Affiliation: Institute for Immunology and Infectious Diseases
Language: English
Resource Type: Journal article
Additional Information: Merrilee Needham and Frank Mastaglia appears as part of the International IBM Genetics Consortium

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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: Geriatrics & Gerontology; Neurosciences
ESI research areas: Neuroscience & Behavior