Interleukin-2 receptor-α proximal promoter hypomethylation is associated with multiple sclerosis

Field, J., Fox, A., Jordan, M.A., Baxter, A.G., Spelman, T., Gresle, M., Butzkueven, H., Kilpatrick, T.J., and Rubio, J.P. (2017) Interleukin-2 receptor-α proximal promoter hypomethylation is associated with multiple sclerosis. Genes and Immunity, 18. pp. 59-66.

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Genetic studies have demonstrated association between single-nucleotide polymorphisms within the IL2RA (interleukin-2 receptor a-subunit) gene and risk of developing multiple sclerosis (MS); however, these variants do not have obvious functional consequences. DNA methylation is a source of genetic variation that could impact on autoimmune disease risk. We investigated DNA methylation of the IL2RA promoter in genomic DNA obtained from peripheral blood mononuclear cells and neural tissue using matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry. A differential methylation profile of IL2RA was identified, suggesting that IL2RA expression was regulated by DNA methylation. We extended our analysis of DNA methylation to peripheral blood mononuclear cell (PBMC) of MS cases and controls using MALDI-TOF and Illumina HumanMethylation450 arrays. Analyses of CpG sites within the proximal promoter of IL2RA in PBMC showed no differences between MS cases and controls despite an increase in IL2RA expression. In contrast, we inferred significant DNA methylation differences specific to particular leukocyte subtypes in MS cases compared with controls by deconvolution of the array data. The decrease in methylation in patients correlated with an increase in IL2RA expression in T cells from MS cases in comparison with controls. Our data suggest that differential methylation of the IL2RA promoter in T cells could be an important pathogenic mechanism in MS.

Item ID: 50335
Item Type: Article (Research - C1)
ISSN: 1476-5470
Funders: National Health and Medical Research Council (NHMRC), Multiple Sclerosis Research Australia (MSRA), Lions International, Rebecca L. Cooper Foundation
Projects and Grants: NHMRC Project Grant no 257518, NHMRC Project Grant no 509184, MSRA Fellowship, NHMRC/MRSA Betty Cuthbert fellowship, NHRMC Research Fellowship
Date Deposited: 20 Sep 2017 07:59
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3204 Immunology > 320406 Immunogenetics (incl. genetic immunology) @ 50%
32 BIOMEDICAL AND CLINICAL SCIENCES > 3209 Neurosciences > 320905 Neurology and neuromuscular diseases @ 50%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920111 Nervous System and Disorders @ 100%
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