Kidney Week

Abstract: TH-OR087

An Investigation into the DNA Methylation Patterns of CKD in Older Individuals

Session Information

• Novel Risk Factors for CKD
  October 25, 2018 | Location: 6E, San Diego Convention Center
  Abstract Time: 05:42 PM - 05:54 PM

Category: Geriatric Nephrology

• 1100 Geriatric Nephrology

Authors

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

Laura Jane Smyth, PhD



Postdoctoral Research Fellow at Queen's University Belfast, Northern Ireland

• Cruise, Sharon, Queen's University Belfast, Belfast, United Kingdom

Sharon Cruise,

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

Jill Kilner,

• Maxwell, Alexander P., Queen's University Belfast, Belfast, United Kingdom

Alexander P. Maxwell,

• Mcguinness, Bernadette, Queen's University Belfast, Belfast, United Kingdom

Bernadette Mcguinness,

• Kee, Frank, Queen's University Belfast, Belfast, United Kingdom

Frank Kee,

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

A.J. Mcknight,

Group or Team Name

• On behalf of the Northern Ireland Cohort of Longitudinal Ageing collaborative group

Background

Changes in DNA methylation are associated with chronic diseases. The study assessed whether methylation status of CpG sites differs between individuals with and without CKD between the ages of 60 and 79.

Methods

Participants were recruited as part of the Northern Ireland COhort for the Longitudinal study of Ageing (NICOLA), a large-scale population-based prospective cohort study. Estimated GFR was calculated for each individual (n=1,097) using the CKD-EPI formula. CKD stages, based on eGFR, were determined and all individuals with stage 2 CKD (eGFR >60 - <90mL/min/1.73m²) were removed to increase discrimination between CKD case and control groups. Using the Infinium HD Methylation Assay, MethylationEPIC BeadChips from Illumina, the methylation status of >850,000 CpG sites, gene bodies, promoters and CpG islands were determined in each individual. Blood-derived DNA was processed consistently within our single genetics centre. Partek Genomics Suite 7.0 was utilised for data analysis, with standard quality control applied. In total, 155 individuals had CKD stages 3, 4 or 5 and were compared with 240 individuals with eGFR >90ml/min/1.73m² and no evidence of renal disease.

Results

In total, 306 CpG sites were identified as having significantly different levels of methylation in individuals with CKD compared with controls (p<1x10^-07). Among the genes identified with altered methylation status, several, including CLU, NOS3, IQSEC1 and NPHP4 have been linked with CKD. High concordance between duplicate samples was also observed for this array. Three of the significantly associated CpG sites demonstrated a graduated increase in the methylation fold change with worsening renal function i.e. comparing control individuals with persons having CKD stages 3, 4 and 5 respectively.

Conclusion

Epigenetic modifications, such as DNA methylation, may represent important biomarkers for the loss of kidney function in individuals with CKD. Data from this longitudinal cohort study provides the opportunity to monitor and assess the relationship between methylation status and CKD over time with a view to identifying new biomarkers or expanding knowledge of those previously identified CKD biomarkers.