2026-07-21T14:00:55Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/127372024-10-31T11:44:57Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Liu, Yuwei
author
Shen, Yu
author
Guo, Tao
author
Parnell, Laurence D.
author
Westerman, Kenneth E.
author
Smith, Caren E.
author
Ordovas, Jose M
author
Lai, Chao-Qiang
funder
China Scholarship Council
funder
United States Department of Agriculture
2021-04-23T07:15:45Z
2021-04-23T07:15:45Z
2020-06-16
Front Genet. 2020; 11:622
10.3389/fgene.2020.00622
1664-8021
1664-8021
Frontiers in Genetics
32612641
http://hdl.handle.net/20.500.12105/12737
Statin is the medication most widely prescribed to reduce plasma cholesterol levels. Yet, how the medication contributes to diabetes risk and impaired glucose metabolism is not clear. This study aims to examine the epigenetic mechanisms of ABCG1 through which statin use associates with risk of type 2 diabetes. We determined the association between the statin use, DNA methylation at ABCG1 and type 2 diabetes/glycemic traits in the Framingham Heart Study Offspring (FHS, n = 2741), with validation in the Women’s Health Initiative Study (WHI, n = 2020). The causal effect of statin use on the risk of type 2 diabetes was examined using a two-step Mendelian randomization approach. Next, based on transcriptome analysis, we determined the links between the medication-associated epigenetic status of ABCG1 and biological pathways on the pathogenesis of type 2 diabetes. Our results showed that DNA methylation levels at cg06500161 of ABCG1 were positively associated with the use of statin, type 2 diabetes and related traits (fasting glucose and insulin) in FHS and WHI. Two-step Mendelian randomization suggested a causal effect of statin use on type 2 diabetes and related traits through epigenetic mechanisms, specifically, DNA methylation at cg06500161. Our results highlighted that gene expression of ABCG1, ABCA1 and ACSL3, involved in both cholesterol metabolism and glycemic pathways, was inversely associated with statin use, CpG methylation, and diabetic signatures. We concluded that DNA methylation site cg06500161 at ABCG1 is a mediator of the association between statins and risk of type 2 diabetes.
eng
Statin
ABCG1
Methylation
Type 2 diabetes
cg06500161
Statin Use Associates With Risk of Type 2 Diabetes via Epigenetic Patterns at ABCG1
journal article
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