#843 Methylation of HMGCR gene promoter in patients on hemodialysis

Abstract

Abstract Background and Aims Patients with chronic kidney disease (CKD) exhibit a pronounced risk for cardiovascular mortality; the most vulnerable group enrolls patients on hemodialysis. Unfortunately no meaningful decrease of cardiovascular risk after cholesterol lowering medication – inhibitors of HMGCR - was demonstrated in hemodialysed patients. The incidence of complications in CKD patients correlates with changed epigenetic mechanisms, the most studied epigenetic phenomenon is DNA methylation. The aim of this study was to elucidate the methylation status of HMGCR gene and evaluate its impact on cardiovascular morbidity and mortality in patients receiving hemodialysis. Method We analyzed DNA in plasma of 21 hemodialyzed patients before and after dialysis. Then bisulfite conversion was carried out to distinguish methylated and unmethylated form of DNA. The primers of HMGCR genes promoters were designed, after that methylation specific PCR and sequential analysis of PCR products were performed. Results Although the methylation rate of HMGCR gene dropped 9 patients during the hemodialysis session, no statistical significance of this demethylation was confirmed. No correlation of methylation status of HMGCR gene and cholesterol or phosphorus was confirmed. Hypomethylated promoter of HMGCR gene was found in 6 patients, who either underwent amputation of lower extremity due to arterial ischemia or has deceased due to cardiovascular event during next 6 month of follow-up period. Conclusion This study suggests that both DNA demethylation and consecutive increased expression of HMGCR gene could be predictors of high risk of cardiovascular morbidity and mortality in hemodialyzed diabetic patients.