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Abstract: TH-PO615

Association of DNA Methylation Signatures With Premature Aging and Cardiovascular Death in Patients With ESKD: A Pilot Study

Session Information

Category: Hypertension and CVD

  • 1501 Hypertension and CVD: Epidemiology‚ Risk Factors‚ and Prevention

Authors

  • Sumida, Keiichi, The University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Mozhui, Khyobeni, The University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Liang, Xiaoyu, The University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Han, Zhongji, The University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Mallisetty, Yamini, The University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Kovesdy, Csaba P., The University of Tennessee Health Science Center, Memphis, Tennessee, United States
Background

Patients with ESKD display features of premature aging, with extremely high cardiovascular (CV) mortality at a younger age. There is strong evidence that changes in DNA methylation (DNAm) contribute to age-related pathologies; however, little is known about their association with premature aging and CV death in patients with ESKD.

Methods

We assayed genome-wide DNAm in a pilot case-control study of 30 hemodialysis (HD) patients who died of CV events as cases and 30 matched HD controls who remained alive during follow-up of 2.0 years. DNAm was profiled on the Illumina EPIC BeadChip. Four established DNAm clocks (i.e., Horvath-, Hannum-, Pheno-, and GrimAge) were used to estimate epigenetic age (DNAmAge), and epigenetic age acceleration (EAA) were derived as the residuals of regressing DNAmAge on chronological age (cAge). An epigenome-wide association study (EWAS) was performed to identify differentially methylated CpGs associated with CV death, adjusted for cAge, sex, race, and top 5 principal components.

Results

Patient characteristics were similar between cases and controls, with a mean age of 63 years, 48% male, and 54% African American in both groups. All clocks performed well at predicting cAge (correlation between DNAmAges and cAge of r=0.76-0.89). GrimAge had the largest absolute deviation from chroAge (mean, +21.3 years) (Figure). There was no significant difference in EAAs between groups. For EWAS, a CpG (cg22305782) in FBXL19 had the strongest association with CV death with significantly lower DNAm in cases vs. controls (PFDR=2.0x10-6). FBXL19 is involved in inflammation, apoptosis, and cell migration.

Conclusion

Overall, we observed more accelerated aging in patient with ESKD, although there was no difference in EAAs between groups. EWAS suggests a potential novel DNAm biomarker for premature CV death in ESKD.

Correlation between cAge and GrimAge in 60 HD patients