Cholesterol lowering treatment restores blood global DNA methylation in chronic kidney disease (CKD) patients

Angelo Zinellu, Salvatore Sotgia, Elisabetta Sotgiu, Stefano Assaretti, Angela Baralla, Arduino Mangoni, Andrea Satta, Ciriaco Carru

    Research output: Contribution to journalArticlepeer-review

    8 Citations (Scopus)

    Abstract

    Background and aims Chronic kidney disease (CKD) is characterized by increased oxidative stress (OS). In consideration of the well-known link between OS and DNA methylation we assessed DNA methylcytosine (mCyt) concentrations in CKD patients at baseline and during cholesterol lowering treatment. Methods and results DNA methylation and OS indices (malonyldialdehyde, MDA; allantoin/uric acid ratio, All/UA) were measured in 30 CKD patients randomized to three cholesterol lowering regimens for 12 months (simvastatin 40 mg/day, ezetimibe/simvastatin 10/20 mg/day, or ezetimibe/simvastatin 10/40 mg/day) and 30 age- and sex-matched healthy controls. DNA methylation was significantly lower in CKD patients vs. controls (4.06 ± 0.20% vs. 4.27 ± 0.17% mCyt, p = 0.0001). Treatment significantly increased mCyt DNA concentrations in all patients (4.06 ± 0.04% at baseline; 4.12 ± 0.03% at 4 months; 4.17 ± 0.03% at 8 months; and 4.20 ± 0.02% at 12 months, p = 0.0001 for trend). A trend for a greater effect on DNA methylation was observed with combined treatment ezetimibe/simvastatin 10/40 mg/day (+5.2% after one year treatment). The treatment-associated mCyt increase was significantly correlated with the concomitant reduction in MDA concentrations and All/AU ratios. Conclusion Our results demonstrate that CKD patients have a lower degree of DNA methylation and that cholesterol lowering treatment restores mCyt DNA concentrations to levels similar to healthy controls. The treatment-associated increase in DNA methylation is correlated with a concomitant reduction in OS markers. The study was registered at clinicaltrials.gov (NCT00861731).

    Original languageEnglish
    Pages (from-to)822-829
    Number of pages8
    JournalNutrition Metabolism and Cardiovascular Diseases
    Volume27
    Issue number9
    DOIs
    Publication statusPublished - Sep 2017

    Keywords

    • Chronic kidney disease
    • DNA methylation
    • Ezetimibe
    • Methylcytosine
    • Oxidative stress
    • Simvastatin

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