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

NEUROBIOLOGY OF AGING

卷:36

Article

Gang, Qiang^1,2  Bettencourt, Conceicao¹  Machado, Pedro M.^1,2  Fox, Zoe^3,4  Brady, Stefen²  Healy, Estelle²  Parton, Matt²  Holton, Janice L.²  Hilton-Jones, David⁵  Shieh, Perry B.⁶  Zanoteli, Edmar⁷  De Paepe, Boel⁸  De Bleecker, Jan⁸  Shaibani, Aziz⁹  Ripolone, Michela¹⁰  Violano, Raffaella¹⁰  Moggio, Maurizio¹⁰  Dimachkie, Mazen M.¹¹  Mora, Marina¹²  Mantegazza, Renato¹²  Zanotti, Simona¹²  Hanna, Michael G.^1,2  Houlden, Henry^1,2 

[1] UCL, Inst Neurol, Dept Mol Neurosci, London, England

[2] UCL, Inst Neurol, Med Res Council, Ctr Neuromuscular Dis, London, England

[3] UCL, Biomed Res Ctr, London, England

[4] UCL, Inst Neurol, Educ Unit, London, England

[5] Univ Oxford, Nuffield Dept Clin Neurosci, Oxford, England

[6] Univ Calif Los Angeles, Dept Neurol, Neuromuscular Div, Med Ctr, Los Angeles, CA 90024 USA

[7] Univ Sao Paulo FMUSP, Sch Med, Dept Neurol, Sao Paulo, Brazil

[8] Ghent Univ Hosp, Dept Neurol & Neuromuscular Reference Ctr, Ghent, Belgium

[9] Nerve & Muscle Ctr Texas, Houston, TX USA

[10] Univ Milan, Neuromuscular Unit, Fdn IRCCS Ca Granda Osped Maggiore Policlin, Dino Ferrari Ctr, Milan, Italy

[11] Univ Kansas, Med Ctr, Lawrence, KS 66045 USA

[12] Fdn IRCCS Isit Neurol C Besta, Neuromuscular Dis & Neuroimmunol Unit, Milan, Italy

关键词: Sporadic inclusion body myositis;    sIBM;    APOE;    TOMM40;    Age of onset;   

DOI  :  10.1016/j.neurobiolaging.2014.12.039

来源: Elsevier

【 摘 要 】

A previous study showed that, in carriers of the apolipoprotein E (APOE) genotype epsilon 3/epsilon 3 or epsilon 3/epsilon 4, 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 epsilon 3/epsilon 3. 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 epsilon 3/epsilon 3. (C) 2015 The Authors. Published by Elsevier Inc.

【 授权许可】

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