title: DNA methylation at IL32 in juvenile idiopathic arthritis.
abstract: Juvenile idiopathic arthritis (JIA) is the most common autoimmune rheumatic disease of childhood. We recently showed that DNA methylation at the gene encoding the pro-inflammatory cytokine interleukin-32 (IL32) is reduced in JIA CD4+ T cells. To extend this finding, we measured IL32 methylation in CD4+ T-cells from an additional sample of JIA cases and age- and sex-matched controls, and found a reduction in methylation associated with JIA consistent with the prior data (combined case-control dataset: 25.0% vs 37.7%, p = 0.0045). Further, JIA was associated with reduced IL32 methylation in CD8+ T cells (15.2% vs 25.5%, p = 0.034), suggesting disease-associated changes to a T cell precursor. Additionally, we measured regional SNPs, along with CD4+ T cell expression of total IL32, and the γ and β isoforms. Several SNPs were associated with methylation. Two SNPs were also associated with JIA, and we found evidence of interaction such that methylation was only associated with JIA in minor allele carriers (e.g. rs10431961 p(interaction) = 0.011). Methylation at one measured CpG was inversely correlated with total IL32 expression (Spearman r = -0.73, p = 0.0009), but this was not a JIA-associated CpG. Overall, our data further confirms that reduced IL32 methylation is associated with JIA, and that SNPs play an interactive role.
authors.affiliation: Genes, Environment &Complex Disease, Murdoch Childrens Research Institute, Parkville, Victoria, Australia.
authors.forename: Braydon
authors.initials: B
authors.lastname: Meyer
authors.affiliation: 1] Genes, Environment &Complex Disease, Murdoch Childrens Research Institute, Parkville, Victoria, Australia [2] Department of Paediatrics, University of Melbourne, Victoria, Australia.
authors.forename: Raul A
authors.initials: RA
authors.lastname: Chavez
authors.affiliation: 1] Arthritis &Rheumatology, Murdoch Childrens Research Institute, Parkville, Victoria, Australia [2] Paediatric Rheumatology Unit, Royal Children's Hospital, Parkville, Victoria, Australia.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Munro
authors.affiliation: 1] Genes, Environment &Complex Disease, Murdoch Childrens Research Institute, Parkville, Victoria, Australia [2] Department of Paediatrics, University of Melbourne, Victoria, Australia.
authors.forename: Rachel C
authors.initials: RC
authors.lastname: Chiaroni-Clarke
authors.affiliation: 1] Arthritis &Rheumatology, Murdoch Childrens Research Institute, Parkville, Victoria, Australia [2] Paediatric Rheumatology Unit, Royal Children's Hospital, Parkville, Victoria, Australia.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Akikusa
authors.affiliation: 1] Arthritis &Rheumatology, Murdoch Childrens Research Institute, Parkville, Victoria, Australia [2] Paediatric Rheumatology Unit, Royal Children's Hospital, Parkville, Victoria, Australia.
authors.forename: Roger C
authors.initials: RC
authors.lastname: Allen
authors.affiliation: 1] Environmental &Genetic Epidemiology Research, Murdoch Childrens Research Institute, Parkville, Victoria, Australia [2] Department of Paediatrics, University of Melbourne, Victoria, Australia.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Craig
authors.affiliation: 1] Environmental &Genetic Epidemiology Research, Murdoch Childrens Research Institute, Parkville, Victoria, Australia [2] Department of Paediatrics, University of Melbourne, Victoria, Australia.
authors.forename: Anne-Louise
authors.initials: AL
authors.lastname: Ponsonby
authors.affiliation: 1] Cancer &Disease Epigenetics, Murdoch Childrens Research Institute, Parkville, Victoria, Australia [2] Department of Paediatrics, University of Melbourne, Victoria, Australia.
authors.forename: Richard
authors.initials: R
authors.lastname: Saffery
authors.affiliation: 1] Genes, Environment &Complex Disease, Murdoch Childrens Research Institute, Parkville, Victoria, Australia [2] Department of Paediatrics, University of Melbourne, Victoria, Australia.
authors.forename: Justine A
authors.initials: JA
authors.lastname: Ellis
mesh_terms: D001171:Arthritis, Juvenile / Q000235:genetics*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D019175:DNA Methylation; D006801:Humans; D007378:Interleukins / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide
chemical_list: C496971:IL32 protein, human; D007378:Interleukins