A Zinellu1, S Sotgia2, E Sotgiu2, S Assaretti2, A Baralla2, A A Mangoni3, A E Satta4, C Carru5. 1. Department of Biomedical Sciences, University of Sassari, Sassari, Italy. Electronic address: azinellu@uniss.it. 2. Department of Biomedical Sciences, University of Sassari, Sassari, Italy. 3. Department of Clinical Pharmacology, School of Medicine, Flinders University, Adelaide, Australia. 4. Department of Surgical, Microsurgical and Medical Sciences, University of Sassari, Sassari, Italy. 5. Department of Biomedical Sciences, University of Sassari, Sassari, Italy; Quality Control Unit, University Hospital Sassari (AOU), Sassari, Italy.
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 threecholesterol 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).
RCT Entities:
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 CKDpatients 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 CKDpatients 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 CKDpatients 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 CKDpatients 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).
Authors: Anna Witasp; Karin Luttropp; Abdul Rashid Qureshi; Peter Barany; Olof Heimbürger; Lars Wennberg; Tomas J Ekström; Paul G Shiels; Peter Stenvinkel; Louise Nordfors Journal: Sci Rep Date: 2022-01-10 Impact factor: 4.379
Authors: Natalia Arias; Silvia Arboleya; Joseph Allison; Aleksandra Kaliszewska; Sara G Higarza; Miguel Gueimonde; Jorge L Arias Journal: Nutrients Date: 2020-08-05 Impact factor: 5.717