Aim: Statins lower cholesterol and reduce the risk of cardiovascular disease. However, the exact mechanisms of statins remain unknown. We investigated whether statin therapy associates with epigenetics in Type 2 diabetes (T2D) patients. Materials & methods: DNA methylation was analyzed in blood from newly diagnosed T2D patients in All New Diabetics in Scania (ANDIS) and a replication cohort All New Diabetics in Uppsala County (ANDiU). Results: Seventy-nine sites were differentially methylated between cases on statins and controls (false discovery rate <5%) in ANDIS. These include previously statin-associated methylation sites annotated to DHCR24 (cg17901584), ABCG1 (cg27243685) and SC4MOL (cg05119988). Differential methylation of two sites related to cholesterol biosynthesis and immune response, cg17901584 (DHCR24) and cg23011663 (ARIH2), were replicated in ANDiU. Conclusion: Statin therapy associates with epigenetic modifications in T2D patients.
Keywords: DNA methylation; HDL; LDL; Type 2 diabetes; cardiovascular disease; causal mediation analyses; epigenetics; pharmacoepigenetics; statins; therapy.