75992 Journal Article.pdf (992.73 kB)
Polymorphisms in the Receptor Tyrosine Kinase MERTK Gene Are Associated with Multiple Sclerosis Susceptibility
journal contribution
posted on 2023-05-17, 10:32 authored by Ma, GZM, Jim Stankovich, Bahlo, M, Booth, DR, Broadley, S, Brown, MA, Browning, BL, Browning, SR, Butzkueven, H, Carroll, WM, Danoy, P, Simon James FooteSimon James Foote, Griffiths, L, Heard, RN, Kermode, AG, Lechner-Scott, J, Moscato, P, Perreau, VM, Scott, RJ, Slee, M, Stewart, GJ, Bruce TaylorBruce Taylor, Wiley, J, Kilpatrick, TJ, Binder, MD, Field, JMultiple 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.
History
Publication title
PL o S OneVolume
6Article number
e16964Number
e16964Pagination
1-6ISSN
1932-6203Department/School
Menzies Institute for Medical ResearchPublisher
Public Library of SciencePlace of publication
United StatesRights statement
Licensed under Creative Commons Attribution 2.5 Generic (CC BY 2.5) http://creativecommons.org/licenses/by/2.5/Repository Status
- Open