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Variation within MBP gene predicts disease course in multiple sclerosis

Citation

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]


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Copyright 2017 the authors

DOI: doi:10.1002/brb3.670

Abstract

Objective: Prognosis following a first demyelinating event is difficult to predict, with no genetic markers of MS progression currently identified. Myelin basic protein (MBP) is a major component of the myelin sheath of CNS neurons and may play a central role in demyelinating diseases such as MS. However, genetic variation in MBP has not been implicated in MS onset risk in large genome-wide association studies. We hypothesized that genetic variations in MBP may be a determinant of MS clinical course.

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 Details

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 Group:Neurosciences
Research Field:Central Nervous System
Objective Division:Health
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)
ID Code:120427
Year Published:2017
Web of Science® Times Cited:3
Deposited By:Menzies Institute for Medical Research
Deposited On:2017-08-24
Last Modified:2018-06-21
Downloads:51 View Download Statistics

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