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Neurological Sciences

, Volume 39, Issue 2, pp 297–304 | Cite as

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

  • Yuan Zhou
  • Ming Chen
  • Steve SimpsonJr
  • Robyn M. Lucas
  • Jac C. Charlesworth
  • Nicholas Blackburn
  • Ingrid van der Mei
  • Anne-Louise Ponsonby
  • Ausimmune/AUSLONG investigators group
  • Bruce V TaylorEmail author
Original Article

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.

Keywords

miR-146a Conversion to MS Relapse EDSS 

Notes

Acknowledgements

The members of the AUSLONG investigators group are as follows: Robyn M Lucas (National Centre for Epidemiology and Population Health, Canberra); Keith Dear (Duke Kunshan University, Kunshan, China); Anne-Louise Ponsonby and Terry Dwyer (Murdoch Children’s Research Institute, Melbourne, Australia); Ingrid van der Mei, Leigh Blizzard, Steve Simpson, Jr., and Bruce V Taylor (Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia); Simon Broadley (School of Medicine, Griffith University, Gold Coast Campus, Australia); Trevor Kilpatrick (Centre for Neurosciences, Department of Anatomy and Neuroscience, University of Melbourne, Melbourne, Australia); David Williams and Jeanette Lechner-Scott (University of Newcastle, Newcastle, Australia); Cameron Shaw and Caron Chapman (Barwon Health, Geelong, Australia); Alan Coulthard (University of Queensland, Brisbane, Australia); and Patricia Valery (QIMR Berghofer Medical Research Institute, Brisbane, Australia).

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Copyright information

© Springer-Verlag Italia S.r.l. 2017

Authors and Affiliations

  • Yuan Zhou
    • 1
  • Ming Chen
    • 2
  • Steve SimpsonJr
    • 1
    • 3
  • Robyn M. Lucas
    • 4
  • Jac C. Charlesworth
    • 1
  • Nicholas Blackburn
    • 1
  • Ingrid van der Mei
    • 1
  • Anne-Louise Ponsonby
    • 5
  • Ausimmune/AUSLONG investigators group
  • Bruce V Taylor
    • 1
    Email author
  1. 1.Menzies Institute for Medical ResearchUniversity of TasmaniaHobartAustralia
  2. 2.Department of Clinical Laboratory, Xinqiao HospitalThird Military Medical UniversityChongqingChina
  3. 3.Melbourne School of Population and Global HealthUniversity of MelbourneMelbourneAustralia
  4. 4.National Centre for Epidemiology and Population Health, Research School of Population HealthThe Australian National UniversityCanberraAustralia
  5. 5.Murdoch Children’s Research InstituteUniversity of MelbourneMelbourneAustralia

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