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 Â± 0.20% vs. 4.27 Â± 0.17% mCyt, p = 0.0001). Treatment significantly increased mCyt DNA concentrations in all patients (4.06 Â± 0.04% at baseline; 4.12 Â± 0.03% at 4 months; 4.17 Â± 0.03% at 8 months; and 4.20 Â± 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).
Cholesterol lowering treatment restores blood global DNA methylation in chronic kidney disease (CKD) patients / Zinellu, Angelo; Sotgia, Salvatore; Sotgiu, Elisabetta; Assaretti, Stefano; Baralla, Angela; Mangoni, A. A.; Satta, Andrea Ercole; Carru, Ciriaco. - In: NMCD. NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES. - ISSN 0939-4753. - (2017). [10.1016/j.numecd.2017.06.011]