Assessment of differentially methylated loci in individuals with end-stage kidney disease attributed to diabetic kidney disease : an exploratory study

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dc.contributor.author Smyth, L. J.
dc.contributor.author Kilner, J.
dc.contributor.author Nair, V.
dc.contributor.author Liu, H.
dc.contributor.author Brennan, E.
dc.contributor.author Kerr, K.
dc.contributor.author Sandholm, N.
dc.contributor.author Cole, J.
dc.contributor.author Dahlström, E.
dc.contributor.author Syreeni, A.
dc.contributor.author Salem, R. M.
dc.contributor.author Nelson, R. G.
dc.contributor.author Looker, H. C.
dc.contributor.author Wooster, C.
dc.contributor.author Anderson, K.
dc.contributor.author McKay, G. J.
dc.contributor.author Kee, F.
dc.contributor.author Young, I.
dc.contributor.author Andrews, D.
dc.contributor.author Forsblom, C.
dc.contributor.author Hirschhorn, J. N.
dc.contributor.author Godson, C.
dc.contributor.author Groop, P. H.
dc.contributor.author Maxwell, A. P.
dc.contributor.author Susztak, K.
dc.contributor.author Kretzler, M.
dc.contributor.author Florez, J. C.
dc.contributor.author McKnight, A. J.
dc.date.accessioned 2022-02-18T10:26:04Z
dc.date.available 2022-02-18T10:26:04Z
dc.date.issued 2021-12
dc.identifier.citation Smyth , L J , Kilner , J , Nair , V , Liu , H , Brennan , E , Kerr , K , Sandholm , N , Cole , J , Dahlström , E , Syreeni , A , Salem , R M , Nelson , R G , Looker , H C , Wooster , C , Anderson , K , McKay , G J , Kee , F , Young , I , Andrews , D , Forsblom , C , Hirschhorn , J N , Godson , C , Groop , P H , Maxwell , A P , Susztak , K , Kretzler , M , Florez , J C & McKnight , A J 2021 , ' Assessment of differentially methylated loci in individuals with end-stage kidney disease attributed to diabetic kidney disease : an exploratory study ' , Clinical epigenetics , vol. 13 , no. 1 , 99 . https://doi.org/10.1186/s13148-021-01081-x
dc.identifier.other PURE: 174274338
dc.identifier.other PURE UUID: a39dd028-7143-447f-98a9-42788830e7ff
dc.identifier.other Scopus: 85105134174
dc.identifier.other PubMed: 33933144
dc.identifier.other ORCID: /0000-0003-4322-6942/work/108464692
dc.identifier.other ORCID: /0000-0003-1857-2560/work/108466582
dc.identifier.other ORCID: /0000-0003-1271-8696/work/108466828
dc.identifier.uri http://hdl.handle.net/10138/340639
dc.description Publisher Copyright: © 2021, The Author(s).
dc.description.abstract Background: A subset of individuals with type 1 diabetes mellitus (T1DM) are predisposed to developing diabetic kidney disease (DKD), the most common cause globally of end-stage kidney disease (ESKD). Emerging evidence suggests epigenetic changes in DNA methylation may have a causal role in both T1DM and DKD. The aim of this exploratory investigation was to assess differences in blood-derived DNA methylation patterns between individuals with T1DM-ESKD and individuals with long-duration T1DM but no evidence of kidney disease upon repeated testing to identify potential blood-based biomarkers. Blood-derived DNA from individuals (107 cases, 253 controls and 14 experimental controls) were bisulphite treated before DNA methylation patterns from both groups were generated and analysed using Illumina’s Infinium MethylationEPIC BeadChip arrays (n = 862,927 sites). Differentially methylated CpG sites (dmCpGs) were identified (false discovery rate adjusted p ≤ × 10–8 and fold change ± 2) by comparing methylation levels between ESKD cases and T1DM controls at single site resolution. Gene annotation and functionality was investigated to enrich and rank methylated regions associated with ESKD in T1DM. Results: Top-ranked genes within which several dmCpGs were located and supported by functional data with methylation look-ups in other cohorts include: AFF3, ARID5B, CUX1, ELMO1, FKBP5, HDAC4, ITGAL, LY9, PIM1, RUNX3, SEPTIN9 and UPF3A. Top-ranked enrichment pathways included pathways in cancer, TGF-β signalling and Th17 cell differentiation. Conclusions: Epigenetic alterations provide a dynamic link between an individual’s genetic background and their environmental exposures. This robust evaluation of DNA methylation in carefully phenotyped individuals has identified biomarkers associated with ESKD, revealing several genes and implicated key pathways associated with ESKD in individuals with T1DM. en
dc.format.extent 19
dc.language.iso eng
dc.relation.ispartof Clinical epigenetics
dc.rights cc_by
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject Association
dc.subject Diabetes
dc.subject End-stage
dc.subject EPIC
dc.subject Kidney
dc.subject Methylation
dc.subject Nephropathy
dc.subject 3121 General medicine, internal medicine and other clinical medicine
dc.title Assessment of differentially methylated loci in individuals with end-stage kidney disease attributed to diabetic kidney disease : an exploratory study en
dc.type Article
dc.contributor.organization Medicum
dc.contributor.organization HUS Abdominal Center
dc.contributor.organization Clinicum
dc.contributor.organization CAMM - Research Program for Clinical and Molecular Metabolism
dc.contributor.organization University of Helsinki
dc.contributor.organization Nefrologian yksikkö
dc.contributor.organization HUS Internal Medicine and Rehabilitation
dc.contributor.organization Institute for Molecular Medicine Finland
dc.contributor.organization Research Programs Unit
dc.contributor.organization Department of Medicine
dc.contributor.organization Per Henrik Groop / Principal Investigator
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.1186/s13148-021-01081-x
dc.relation.issn 1868-7075
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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