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Common genetic variation within miR-146a predicts disease onset and relapse in multiple sclerosis

Citation

Zhou, Y and Chen, M and Simpson Jr, S and Lucas, RM and Charlesworth, JC and Blackburn, N and van der Mei, I and Ponsonby, A-L and Taylor, BV, Ausimmune/AUSLONG investigators group, Common genetic variation within miR-146a predicts disease onset and relapse in multiple sclerosis, Neurological Sciences, 39, (2) pp. 297-304. ISSN 1590-1874 (2018) [Refereed Article]

Copyright Statement

Copyright Springer-Verlag Italia S.r.l. 2017

DOI: doi:10.1007/s10072-017-3177-1

Abstract

Despite extensive studies focusing on the changes in expression of microRNAs (miRNAs) in multiple sclerosis (MS) compared to healthy controls, few studies have evaluated the association of genetic variants of miRNAs with MS clinical course. We investigated whether a functional polymorphism in the MS associated miR-146a gene predicted clinical course (hazard of conversion to MS and of relapse, and annualized change in disability), using a longitudinal cohort study of persons with a first demyelinating event followed up to their 5-year review. We found the genotype (GC+CC) of rs2910164 predicted relapse compared with the GG genotype (HR=2.09 (95% CI 1.42, 3.06), p=0.0001), as well as a near-significant (p=0.07) association with MS conversion risk. Moreover, we found a significant additive interaction between rs2910164 and baseline anti-EBNA-1 IgG titers predicting risk of conversion to MS (relative excess risk due to interaction [RERI] 2.39, p=0.00002) and of relapse (RERI 1.20, p=0.006). Supporting these results, similar results were seen for the other EBV-correlated variables: anti-EBNA-2 IgG titers and past history of infectious mononucleosis. There was no association of rs2910164 genotype for disability progression. Our findings provide evidence for miR-146a and EBV infection in modulating MS clinical course.

Item Details

Item Type:Refereed Article
Keywords:conversion to MS, EDSS, relapse, miR-146a
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:Blackburn, N (Mr Nicholas Blackburn)
Author:van der Mei, I (Associate Professor Ingrid van der Mei)
Author:Taylor, BV (Professor Bruce Taylor)
ID Code:123886
Year Published:2018 (online first 2017)
Web of Science® Times Cited:1
Deposited By:Menzies Institute for Medical Research
Deposited On:2018-01-31
Last Modified:2018-07-23
Downloads:0

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