Kidney Week

Abstract: FR-OR49

Epigenome-Wide Microarray Analysis of Pre- and Post-Transplant Methylation Profiles in Kidney Transplant Recipients

Session Information

• In-Depth Look at Transplantation: Basic and Translational
  October 23, 2020 | Location: Simulive
  Abstract Time: 05:00 PM - 07:00 PM

Category: Transplantation

• 1901 Transplantation: Basic

Authors

• Kerr, Katie, Queen's University Belfast, Belfast, Belfast, United Kingdom

Katie Kerr



Katie Kerr is a final year PhD student researching the effectiveness of innovative omic technologies for disease research, within the Molecular Epidemiology and Public Health team at Queen’s University Belfast. Throughout her PhD, Katie has developed a particular interest in nephrology and to this end she has published a systematic review highlighting DNA methylation for inherited renal diseases, in addition to a scoping review and protocol for conducting multi-omic disease research. She has also conducted integrated epigenomic and transcriptomic analysis on kidney transplant recipients to identify multi-omic markers of chronic kidney disease, which was presented at the American Society of Human Genetics international conference in Houston (USA) in 2019. Currently, Katie is working with the 100,000 Genomes Project in Northern Ireland to conduct omic analysis to improve diagnostic rates of rare renal phenotypes. Her novel work on the epigenome wide analysis of pre- and post-transplant methylation profiles hopes to highlight epigenetic changes resulting from kidney transplantation to ultimately improve patient outcomes.

• Smyth, Laura Jane, Queen's University Belfast, Belfast, Belfast, United Kingdom

Laura Jane Smyth,

• Kilner, Jill, Queen's University Belfast, Belfast, Belfast, United Kingdom

Jill Kilner,

• Maxwell, Alexander P., Belfast City Hospital Nephrology Service, Belfast, United Kingdom

Alexander P. Maxwell,

• Mcaneney, Helen, Queen's University Belfast, Belfast, Belfast, United Kingdom

Helen Mcaneney,

• Mcknight, A.J., Queen's University Belfast, Belfast, Belfast, United Kingdom

A.J. Mcknight,

Background

Kidney transplantation is the optimal treatment for suitable individuals with end-stage kidney disease (ESKD). Serious post-transplant complications include infections, cardiovascular events, malignancy, and new onset of diabetes after transplant (NODAT). Our regional nephrology centre has the highest living kidney donor transplant rate per million population in Europe, and promotes research to improve patient outcomes. We compared pre and post-transplant methylation profiles in samples derived from matched participants.

Methods

Epigenome-wide analysis was conducted using the Illumina Infinium MethylationEPIC array to interrogate 862,987 sites across the genome and identify any differentially methylated regions (DMR) in samples derived from peripheral blood mononuclear cells of age and sex matched pre (n=25) and post (n=25) kidney transplant recipients. DNA was extracted in a uniform manner and stored carefully undergoing minimal freeze thaw cycles. Samples were run on the same instrument and regression calibration was performed in R to estimate leukocyte cell proportions.

Results

Association analysis using Partek® GenomicsSuite® identified 53 DMR (FDR adjusted p≤0.1 x 10^-8, fold change +/-2). Within the top ranked CpG probes we identified DMR within genes dysregulated in melanoma (e.g. EXOC2, VEPH1), genes encoding extracellular matrix proteins that could influence structural glomerular changes (e.g. SPAM1) and genes with prior chronic kidney disease associations (e.g. FNTA). A DMR was also identified within the long intergenic non-protein coding RNA LINC01544, suggesting possible regulatory function. Additionally, Partek® Pathway™ identified enrichment of DMR in the mitogen-activated protein kinase (MAPK) signalling pathway, primarily implicated in malignancy but also ESKD and cardiovascular disease. Gene ontology analysis identified enrichment of terms associated with localization and binding within cells.

Conclusion

This analysis provides a novel epigenomic perspective on molecular changes caused by kidney transplantation, and highlights markers that may be of relevance to post-transplant complications. We provide evidence supporting further methylation and transcriptomic analyses in larger cohorts to help identify epigenetic risk factors associated with post-transplant complications.