Statin therapy is associated with epigenetic modifications in individuals with Type 2 diabetes

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Statin therapy is associated with epigenetic modifications in individuals with Type 2 diabetes. / Schrader, Silja; Perfilyev, Alexander; Martinell, Mats; García-Calzón, Sonia; Ling, Charlotte.

In: Epigenomics, Vol. 13, No. 12, 01.06.2021, p. 919-925.

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T1 - Statin therapy is associated with epigenetic modifications in individuals with Type 2 diabetes

AU - Schrader, Silja

AU - Perfilyev, Alexander

AU - Martinell, Mats

AU - García-Calzón, Sonia

AU - Ling, Charlotte

PY - 2021/6/1

Y1 - 2021/6/1

N2 - 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.

AB - 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.

KW - cardiovascular disease

KW - causal mediation analyses

KW - DNA methylation

KW - epigenetics

KW - HDL

KW - LDL

KW - pharmacoepigenetics

KW - statins

KW - therapy

KW - Type 2 diabetes

UR - http://www.scopus.com/inward/record.url?scp=85106462654&partnerID=8YFLogxK

U2 - 10.2217/epi-2020-0442

DO - 10.2217/epi-2020-0442

M3 - Article

C2 - 33947200

AN - SCOPUS:85106462654

VL - 13

SP - 919

EP - 925

JO - Epigenomics

JF - Epigenomics

SN - 1750-192X

IS - 12

ER -