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Variation within MBP gene predicts disease course in multiple sclerosis
Yuan Zhou1, Steve Simpson1, Jac C Charlesworth1
1Menzies Institute for Medical Research University of Tasmania Hobart TAS Australia.
Brain and Behavior
|April 18, 2017
Summary
Genetic variations in the Myelin Basic Protein (MBP) gene may predict Multiple Sclerosis (MS) progression. A specific MBP variant (rs12959006) was linked to increased relapse risk and disability, and interacted with viral factors.
Area of Science:
- Neuroimmunology
- Genetics of Neurological Disorders
- Myelin Biology
Background:
- Prognosis after a first demyelinating event, indicative of potential Multiple Sclerosis (MS), is challenging to predict.
- Currently, no genetic markers reliably forecast MS progression.
- Myelin Basic Protein (MBP) is crucial for myelin sheath integrity and implicated in demyelinating diseases like MS, yet its genetic role in MS onset remains unclear.
Purpose of the Study:
- To investigate if genetic variations within the Myelin Basic Protein (MBP) gene influence the clinical course of Multiple Sclerosis (MS).
- To determine if MBP gene variations impact conversion to MS, relapse rates, and disability progression.
- To explore potential interactions between MBP gene variants and environmental factors in MS pathogenesis.
Main Methods:
- A prospective longitudinal cohort study followed 127 individuals after their first demyelinating event for up to 5 years.
- Genotyping was performed to analyze variations in the MBP gene.
- Clinical outcomes, including conversion to MS, relapse occurrence, and annualized disability change, were assessed.
Main Results:
- A specific MBP gene variant, rs12959006, was significantly associated with worse clinical outcomes.
- Carriers of the risk genotype (CT + TT) showed a higher hazard of relapse (HR=1.74) and greater annualized disability progression (β=0.18).
- Significant interactions were observed between the risk genotype and baseline anti-HHV6 IgG levels in predicting MS and relapse, suggesting a combined effect with viral factors. Functional analysis indicated the variant is targeted by transcription factors and microRNAs (miR-218, miR-188-3p).
Conclusions:
- Genetic variations in the Myelin Basic Protein (MBP) gene can predict the clinical course of Multiple Sclerosis (MS).
- The identified MBP variant (rs12959006) directly influences MS progression and interacts with environmental factors like HHV6 infection.
- These findings offer new insights into the genetic determinants of MS progression and highlight potential therapeutic targets.