- Title
- Variation within MBP gene predicts disease course in multiple sclerosis
- Creator
- Zhou, Yuan; Simpson Jr, Steve; Taylor, Bruce V.; Charlesworth, Jac C.; van der Mei, Ingrid; Lucas, Robyn M.; Ponsonby, Anne-Louise; Taylor, Anne-Louise; AUSLONG Investigators Group,; Williams, David; Lechner-Scott, Jeanette
- Relation
- Brain and Behavior Vol. 7, Issue 4, no. e00670
- Publisher Link
- http://dx.doi.org/10.1002/brb3.670
- Publisher
- John Wiley & Sons
- Resource Type
- journal article
- Date
- 2017
- Description
- 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 (ß = 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 (pinteraction = 0.05) and relapse (pinteraction = 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.
- Subject
- clinically definite MS; expanded disability status scale; genetics and single-nucleotide; polymorphism; myelin basic protein; relapse
- Identifier
- http://hdl.handle.net/1959.13/1400090
- Identifier
- uon:34728
- Identifier
- ISSN:2162-3279
- Rights
- © 2017 The Authors. Brain and Behavior published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Language
- eng
- Full Text
- Reviewed
- Hits: 13064
- Visitors: 12235
- Downloads: 290
| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | ATTACHMENT02 | Publisher version (open access) | 373 KB | Adobe Acrobat PDF | View Details Download |