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Polymorphisms in the Receptor Tyrosine Kinase MERTK Gene Are Associated with Multiple Sclerosis Susceptibility

Citation

Ma, GZM and Stankovich, J and Bahlo, M and Booth, DR and Broadley, S and Brown, MA and Browning, BL and Browning, SR and Butzkueven, H and Carroll, WM and Danoy, P and Foote, SJ and Griffiths, L and Heard, RN and Kermode, AG and Lechner-Scott, J and Moscato, P and Perreau, VM and Scott, RJ and Slee, M and Stewart, GJ and Taylor, BV and Wiley, J and Kilpatrick, TJ and Binder, MD and Field, J, Polymorphisms in the Receptor Tyrosine Kinase MERTK Gene Are Associated with Multiple Sclerosis Susceptibility, PL o S One, 6, (2) Article e16964. ISSN 1932-6203 (2011) [Refereed Article]


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Licensed under Creative Commons Attribution 2.5 Generic (CC BY 2.5) http://creativecommons.org/licenses/by/2.5/

DOI: doi:10.1371/journal.pone.0016964

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 1025 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.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Clinical Sciences
Research Field:Medical Genetics (excl. Cancer Genetics)
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Skeletal System and Disorders (incl. Arthritis)
UTAS Author:Stankovich, J (Dr Jim Stankovich)
UTAS Author:Foote, SJ (Professor Simon Foote)
UTAS Author:Taylor, BV (Professor Bruce Taylor)
ID Code:75992
Year Published:2011
Web of Science® Times Cited:21
Deposited By:Menzies Institute for Medical Research
Deposited On:2012-02-22
Last Modified:2017-10-06
Downloads:261 View Download Statistics

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