Zhou, Y and Simpson Jr, S and Charlesworth, JC and van der Mei, I and Lucas, RM and Ponsonby, A-L and Taylor, BV, AUSLONG Investigators Group, Variation within MBP gene predicts disease course in multiple sclerosis, Brain and Behavior, 7, (4) Article e00670. ISSN 2162-3279 (2017) [Refereed Article]
Copyright 2017 the authors
Materials and Methods: We investigated whether variations in the MBP gene altered clinical course (conversion to MS and/or relapse, and annualized change in disability), using a prospectively collected longitudinal cohort study of 127 persons who had had a first demyelinating event, followed up to the 5-year review.
Results: We found one variant, rs12959006, predicted worse clinical outcomes. The risk genotype (CT + TT) was significantly associated with hazard of relapse (HR = 1.74, 95% CI = 1.19-2.56, p = .005) and of greater annualized disability progression (β = 0.18, 95% CI = 0.06-0.30, p = .004). We also found a significant interaction between the risk genotype and baseline anti-HHV6 IgG in predicting MS (ρinteraction = 0.05) and relapse (ρinteraction = 0.02). Functional prediction analysis showed this variant is the target of many transcription factors and the binding sites of miR-218 and miR-188-3p.
Conclusions: Our results provide novel insights into the role of genetic variation within the MBP gene predicting MS clinical course, both directly and by interaction with known environmental MS risk factors.
|Item Type:||Refereed Article|
|Keywords:||clinically definite MS, expanded disability status scale, genetics and single‐nucleotide polymorphism, myelin basic protein, relapse|
|Research Division:||Medical and Health Sciences|
|Research Field:||Central Nervous System|
|Objective Group:||Clinical Health (Organs, Diseases and Abnormal Conditions)|
|Objective Field:||Nervous System and Disorders|
|Author:||Zhou, Y (Mr Yuan Zhou)|
|Author:||Simpson Jr, S (Dr Steve Simpson JR)|
|Author:||Charlesworth, JC (Dr Jac Charlesworth)|
|Author:||van der Mei, I (Associate Professor Ingrid van der Mei)|
|Author:||Taylor, BV (Professor Bruce Taylor)|
|Web of Science® Times Cited:||3|
|Deposited By:||Menzies Institute for Medical Research|
|Downloads:||51 View Download Statistics|
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