Longitudinal Epigenome-Wide Analysis of Kidney Transplant Recipients Pretransplant and Posttransplant

Laura J Smyth; Katie R Kerr; Jill Kilner; Áine E McGill; Alexander P Maxwell; Amy Jayne McKnight

doi:10.1016/j.ekir.2022.11.001

Longitudinal Epigenome-Wide Analysis of Kidney Transplant Recipients Pretransplant and Posttransplant

Kidney Int Rep. 2022 Nov 14;8(2):330-340. doi: 10.1016/j.ekir.2022.11.001. eCollection 2023 Feb.

Authors

Laura J Smyth¹, Katie R Kerr¹, Jill Kilner¹, Áine E McGill¹, Alexander P Maxwell¹, Amy Jayne McKnight¹

Affiliation

¹ Centre for Public Health, Queen's University Belfast, Belfast, Northern Ireland, UK.

Abstract

Introduction: Kidney transplantation remains the gold standard of treatment for end-stage renal disease (ESRD), with improved patient outcomes compared with dialysis. Epigenome-Wide Association Analysis (EWAS) of DNA methylation may identify markers that contribute to an individual's risk of adverse transplant outcomes, yet only a limited number of EWAS have been conducted in kidney transplant recipients. This EWAS aimed to interrogate the methylation profile of a kidney transplant recipient cohort with minimal posttransplant complications, exploring differences in samples pretransplant and posttransplant.

Methods: We compared differentially methylated cytosine-phosphate-guanine sites (dmCpGs) in samples derived from peripheral blood mononuclear cells of the same kidney transplant recipients, collected both pretransplant and posttransplant (N = 154), using the Infinium MethylationEPIC microarray (Illumina, San Diego, CA). Recipients received kidneys from deceased donors and had a mean of 17 years of follow-up.

Results: Five top-ranked dmCpGs were significantly different at false discovery rate (FDR) adjusted P ≤ 9 × 10^-8; cg23597162 within JAZF1, cg25187293 within BTNL8, cg17944885, located between ZNF788P and ZNF625-ZNF20, cg14655917 located between ASB4 and PDK4 and cg09839120 located between GIMAP6 and EIF2AP3.

Conclusion: Five dmCpGs were identified at the generally accepted EWAS critical significance level of FDR adjusted P (P _FDRadj) ≤ 9 × 10^-8, including cg23597162 (within JAZF1) and cg17944885, which have prior associations with chronic kidney disease (CKD). Comparing individuals with no evidence of posttransplant complications (N = 105) demonstrated that 693,555 CpGs (89.57%) did not display any significant difference in methylation (P _FDRadj ≥ 0.05), thereby this study establishes an important reference for future epigenetic studies that seek to identify markers of posttransplant complications.

Keywords: DNA methylation; chronic kidney disease; epigenetics; epigenome-wide association study; kidney transplant.

Abstract

Grants and funding