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• W2308915566 endingPage "e1005853" @default.
• W2308915566 startingPage "e1005853" @default.
• W2308915566 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." @default.
• W2308915566 created "2016-06-24" @default.
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• W2308915566 date "2016-03-18" @default.
• W2308915566 modified "2023-09-26" @default.
• W2308915566 title "Common and Low Frequency Variants in MERTK Are Independently Associated with Multiple Sclerosis Susceptibility with Discordant Association Dependent upon HLA-DRB1*15:01 Status" @default.
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• W2308915566 doi "https://doi.org/10.1371/journal.pgen.1005853" @default.
• W2308915566 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4798184" @default.
• W2308915566 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/26990204" @default.
• W2308915566 hasPublicationYear "2016" @default.
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