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Download fileVariation within MBP gene predicts disease course in multiple sclerosis
journal contribution
posted on 2017-04-01, 00:00 authored by Y Zhou, S Simpson, J C Charlesworth, I van der Mei, R M Lucas, A-L Ponsonby, AUSLONG Investigators Group, B V Taylor, Cameron ShawCameron ShawOBJECTIVE: 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 (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.
History
Journal
Brain and behaviorVolume
7Issue
4Article number
e00670Pagination
1 - 6Publisher
John Wiley & SonsLocation
Chichester, Eng.Publisher DOI
Link to full text
eISSN
2162-3279Language
engPublication classification
C1.1 Refereed article in a scholarly journal; C Journal articleCopyright notice
2017, The AuthorsUsage metrics
Categories
Keywords
clinically definite MSexpanded disability status scalegenetics and single‐nucleotide polymorphismmyelin basic proteinrelapseCase-Control StudiesDisease ProgressionGenetic Predisposition to DiseaseGenetic VariationGenotyping TechniquesHerpesvirus 6, HumanImmunoglobulin GKaplan-Meier EstimateLongitudinal StudiesMultiple SclerosisPrognosisProportional Hazards ModelsProspective StudiesRiskSeverity of Illness IndexAUSLONG Investigators Group