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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Epigenetic link between statin therapy and type 2 diabetes.
Diabetes Care 43, 875-884 (2020)
Verlagsversion
Forschungsdaten
DOI
PMC
OBJECTIVE To investigate the role of epigenetics in statins' diabetogenic effect comparing DNA methylation (DNAm) between statin users and nonusers in an epigenome-wide association study in blood. RESEARCH DESIGN AND METHODS Five cohort studies' participants (n = 8,270) were classified as statin users when they were on statin therapy at the time of DNAm assessment with Illumina 450K or EPIC array or noncurrent users otherwise. Associations of DNAm with various outcomes like incident type 2 diabetes, plasma glucose, insulin, and insulin resistance (HOMA of insulin resistance [HOMA-IR]) as well as with gene expression were investigated. RESULTS Discovery (n = 6,820) and replication (n = 1,450) phases associated five DNAm sites with statin use: cg17901584 (1.12 x 10(-25) [DHCR24]), cg10177197 (3.94 x 10(-08) [DHCR24]), cg06500161 (2.67 x 10(-23) [ABCG1]), cg27243685 (6.01 x 10(-09) [ABCG1]), and cg05119988 (7.26 x 10(-12) [SC4MOL]). Two sites were associated with at least one glycemic trait or type 2 diabetes. Higher cg06500161 methylation was associated with higher fasting glucose, insulin, HOMA-IR, and type 2 diabetes (odds ratio 1.34 [95% CI 1.22, 1.47]). Mediation analyses suggested that ABCG1 methylation partially mediates the effect of statins on high insulin and HOMA-IR. Gene expression analyses showed that statin exposure and ABCG1 methylation were associated with ABCG1 downregulation, suggesting epigenetic regulation of ABCG1 expression. Further, outcomes insulin and HOMA-IR were significantly associated with ABCG1 expression. CONCLUSIONS This study sheds light on potential mechanisms linking statins with type 2 diabetes risk, providing evidence on DNAm partially mediating statins' effects on insulin traits. Further efforts shall disentangle the molecular mechanisms through which statins may induce DNAm changes, potentially leading to ABCG1 epigenetic regulation.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Times Cited
Scopus
Cited By
Cited By
Altmetric
16.019
4.581
14
22
Anmerkungen
Besondere Publikation
Auf Hompepage verbergern
Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Cardiovascular-disease Prevention; Dna Methylation; Cellular Cholesterol; European Guidelines; Ldl-cholesterol; Increased Risk; Abcg1; Desmosterolosis; Identification; Metaanalysis
Sprache
englisch
Veröffentlichungsjahr
2020
HGF-Berichtsjahr
2020
ISSN (print) / ISBN
0149-5992
e-ISSN
1935-5548
Zeitschrift
Diabetes Care
Quellenangaben
Band: 43,
Heft: 4,
Seiten: 875-884
Verlag
American Diabetes Association
Verlagsort
Alexandria, Va.
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Epidemiology (EPI)
Institute of Genetic Epidemiology (IGE)
Institute of Genetic Epidemiology (IGE)
POF Topic(s)
30202 - Environmental Health
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Forschungsfeld(er)
Genetics and Epidemiology
PSP-Element(e)
G-504000-002
G-504091-001
G-504100-001
G-504000-006
G-504090-001
G-504091-001
G-504100-001
G-504000-006
G-504090-001
WOS ID
WOS:000521985600031
Scopus ID
85082147382
PubMed ID
32033992
Erfassungsdatum
2020-03-23