Polymorphisms in the receptor tyrosine kinase MERTK gene are associated with Multiple Sclerosis susceptibility

Ma, G.Z.M., Stankovich, J., Kilpatrick, T.J., Binder, M.D., Field, J., Bahlo, M., Booth, D.R., Broadley, S., Brown, M.A., Browning, B.L., Browning, S.R., Butzkueven, H., Carroll, W.M., Danoy, P., Foote, S.J., Griffiths, L.R., Heard, R.N., Kermode, A.G., Kilpatrick, T.J., Lechner-Scott, J., Moscato, P., Perreau, V.M., Scott, R.J., Slee, M., Stewart, G.J., Taylor, B.V., & Wiley, J. (2011) Polymorphisms in the receptor tyrosine kinase MERTK gene are associated with Multiple Sclerosis susceptibility. PLoS ONE, 6(2).

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Abstract

Multiple sclerosis (MS) is a debilitating, chronic demyelinating disease of the central nervous system affecting over 2 million people worldwide. The TAM family of receptor tyrosine kinases (TYRO3, AXL and MERTK) have been implicated as important players during demyelination in both animal models of MS and in the human disease. We therefore conducted an association study to identify single nucleotide polymorphisms (SNPs) within genes encoding the TAM receptors and their ligands associated with MS. Analysis of genotype data from a genome-wide association study which consisted of 1618 MS cases and 3413 healthy controls conducted by the Australia and New Zealand Multiple Sclerosis Genetics Consortium (ANZgene) revealed several SNPs within the MERTK gene (Chromosome 2q14.1, Accession Number NG_011607.1) that showed suggestive association with MS. We therefore interrogated 28 SNPs in MERTK in an independent replication cohort of 1140 MS cases and 1140 healthy controls. We found 12 SNPs that replicated, with 7 SNPs showing p-values of less than 10-5 when the discovery and replication cohorts were combined. All 12 replicated SNPs were in strong linkage disequilibrium with each other. In combination, these data suggest the MERTK gene is a novel risk gene for MS susceptibility. © 2011 Ma et al.

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ID Code: 87617
Item Type: Journal Article
Refereed: Yes
Keywords: protein AXL, protein MERTK, protein TYRO3, protein tyrosine kinase, tyrosine kinase receptor, unclassified drug, MERTK protein, human, oncoprotein, adult, article, Australia, chromosome 2q, cohort analysis, controlled study, female, gene linkage disequilibrium, gene replication, genetic association, genetic code, genetic identification, genetic risk, genetic susceptibility, genotype, human, major clinical study, male, multiple sclerosis, New Zealand, nucleotide sequence, single nucleotide polymorphism, case control study, genetic predisposition, genetics, Animalia, Case-Control Studies, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Proto-Oncogene Proteins, Receptor Protein-Tyrosine Kinases
DOI: 10.1371/journal.pone.0016964
ISSN: 1932-6203
Divisions: Current > Schools > School of Biomedical Sciences
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2011 The authors
Deposited On: 21 Sep 2015 07:04
Last Modified: 24 Nov 2016 02:52

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