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Common and Low Frequency Variants in MERTK Are Independently Associated with Multiple Sclerosis Susceptibility with Discordant Association Dependent upon HLA-DRB1*15:01 Status.
PLoS Genet
  • Michele D Binder, The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia.
  • Andrew D Fox, The Florey Institute of Neuroscience and Mental Health
  • Daniel Merlo, University of Melbourne
  • Laura J Johnson, The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia.
  • Lauren Giuffrida, University of Melbourne
  • Sarah E Calvert, The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia.
  • Rainer Akkermann, University of Melbourne
  • Gerry Z M Ma, The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia.
  • ANZgene consortium inc Lotti Tajouri (Bond University)
  • Ashwyn A Perera, The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia.
  • Melissa M Gresle, University of Melbourne
  • Louise Laverick, University of Melbourne
  • Grace Foo, University of Melbourne
  • Marzena J Fabis-Pedrini, Western Australian Neuroscience Research Institute
  • Timothy Spelman, University of Melbourne
  • Margaret A Jordan, James Cook University Australia
  • Alan G Baxter, James Cook University Australia
  • Simon Foote, Australian National University
  • Helmut Butzkueven, University of Melbourne
  • Trevor J Kilpatrick, The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia.
  • Judith Field, The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia.
Date of this Version
3-1-2016
Document Type
Journal Article
MeSH Headings (Medical Subject Headings)
ARRAY(0x7f993f8b0a40)
Publication Details

Published version

Binder, M.D., Fox, A.D., Merlo, D., Johnson, L.J., Giuffrida, L., Calvert, S.E., Akkermann, R., Ma, G.Z., ANZgene consorium inc Lotti Tajouri, Perera, A.A., Gresle, M.M., Laverick, L., Foo, G., Fabis-Pedrini, M.J., Spelman, T., Jordan, M.A., Baxter, A.G., Foote, S., Butzkueven, H., Kilpatrick, T.J., Field, J. (2016). Common and low frequency variants in MERTK are independently associated with Multiple Sclerosis susceptibility with discordant association dependent upon HLA-DRB1*15:01 status. PLoS Genet, 12(3), e1005853.

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© 2016 Binder et al.

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Creative Commons Attribution 4.0
Abstract
Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. The risk of developing MS is strongly influenced by genetic predisposition, and over 100 loci have been established as associated with susceptibility. However, the biologically relevant variants underlying disease risk have not been defined for the vast majority of these loci, limiting the power of these genetic studies to define new avenues of research for the development of MS therapeutics. It is therefore crucial that candidate MS susceptibility loci are carefully investigated to identify the biological mechanism linking genetic polymorphism at a given gene to the increased chance of developing MS. MERTK has been established as an MS susceptibility gene and is part of a family of receptor tyrosine kinases known to be involved in the pathogenesis of demyelinating disease. In this study we have refined the association of MERTK with MS risk to independent signals from both common and low frequency variants. One of the associated variants was also found to be linked with increased expression of MERTK in monocytes and higher expression of MERTK was associated with either increased or decreased risk of developing MS, dependent upon HLA-DRB1*15:01 status. This discordant association potentially extended beyond MS susceptibility to alterations in disease course in established MS. This study provides clear evidence that distinct polymorphisms within MERTK are associated with MS susceptibility, one of which has the potential to alter MERTK transcription, which in turn can alter both susceptibility and disease course in MS patients.
Citation Information
Michele D Binder, Andrew D Fox, Daniel Merlo, Laura J Johnson, et al.. "Common and Low Frequency Variants in MERTK Are Independently Associated with Multiple Sclerosis Susceptibility with Discordant Association Dependent upon HLA-DRB1*15:01 Status." PLoS Genet Vol. 12 Iss. 3 (2016) p. 1005853 - 1005853 ISSN: 1553-7404
Available at: http://works.bepress.com/lotti_tajouri/39/