Supplementary Table 4. Statin therapy is associated with epigenetic modifications in individuals with type 2 diabetes

ABSTRACT

Aim: Statins lower cholesterol and reduce the
risk of cardiovascular disease. However, the exact mechanisms of statins remain
unknown. We investigated whether statin therapy associate with epigenetics in
type 2 diabetes (T2D) patients. Material & Methods: DNA methylation was
analysed in blood from newly diagnosed T2D patients from ANDIS and in a
replication cohort (ANDiU). Results: 79 sites were differentially methylated
between cases on statins and controls (FDR<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.

摘要

研究目的：他汀类药物可降低血清胆固醇水平，减少心血管疾病的发病风险，但其确切的作用机制仍未明确。本研究旨在探究他汀类药物治疗与2型糖尿病（T2D）患者表观遗传学的关联。

材料与方法：对来自ANDIS队列的新诊断2型糖尿病患者的血液样本，以及验证队列ANDiU，开展DNA甲基化水平分析。

研究结果：在ANDIS队列中，服用他汀类药物的病例组与对照组间共鉴定出79个差异甲基化位点（错误发现率（False Discovery Rate, FDR）<5%），其中包含此前已报道的与他汀类药物相关的、注释到DHCR24、ABCG1及SC4MOL基因的甲基化位点，具体位点分别为cg17901584（DHCR24）、cg27243685（ABCG1）与cg05119988（SC4MOL）。另有两个与胆固醇生物合成及免疫应答相关的差异甲基化位点——cg17901584（DHCR24）与cg23011663（ARIH2），在ANDiU队列中得到了有效验证。

研究结论：他汀类药物治疗与2型糖尿病患者的表观遗传修饰存在显著关联。