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000153653 1001_ $$00000-0001-8048-9165$$aOchoa-Rosales, Carolina$$b0
000153653 245__ $$aEpigenetic Link Between Statin Therapy and Type 2 Diabetes.
000153653 260__ $$aAlexandria, Va.$$bAssoc.$$c2020
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000153653 500__ $$a2020 Apr;43(4):875-884
000153653 520__ $$aTo investigate the role of epigenetics in statins' diabetogenic effect comparing DNA methylation (DNAm) between statin users and nonusers in an epigenome-wide association study in blood.Five cohort studies' participants (n = 8,270) were classified as statin users when they were on statin therapy at the time of DNAm assessment with Illumina 450K or EPIC array or noncurrent users otherwise. Associations of DNAm with various outcomes like incident type 2 diabetes, plasma glucose, insulin, and insulin resistance (HOMA of insulin resistance [HOMA-IR]) as well as with gene expression were investigated.Discovery (n = 6,820) and replication (n = 1,450) phases associated five DNAm sites with statin use: cg17901584 (1.12 × 10-25 [DHCR24]), cg10177197 (3.94 × 10-08 [DHCR24]), cg06500161 (2.67 × 10-23 [ABCG1]), cg27243685 (6.01 × 10-09 [ABCG1]), and cg05119988 (7.26 × 10-12 [SC4MOL]). Two sites were associated with at least one glycemic trait or type 2 diabetes. Higher cg06500161 methylation was associated with higher fasting glucose, insulin, HOMA-IR, and type 2 diabetes (odds ratio 1.34 [95% CI 1.22, 1.47]). Mediation analyses suggested that ABCG1 methylation partially mediates the effect of statins on high insulin and HOMA-IR. Gene expression analyses showed that statin exposure and ABCG1 methylation were associated with ABCG1 downregulation, suggesting epigenetic regulations of ABCG1 expression. Further, outcomes insulin and HOMA-IR were significantly associated with ABCG1 expression.This study sheds light on potential mechanisms linking statins with type 2 diabetes risk, providing evidence on DNAm partially mediating statins' effects on insulin traits. Further efforts shall disentangle the molecular mechanisms through which statins may induce DNAm changes, potentially leading to ABCG1 epigenetic regulation.
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000153653 7001_ $$aPortilla-Fernandez, Eliana$$b1
000153653 7001_ $$00000-0003-4731-5491$$aNano, Jana$$b2
000153653 7001_ $$aWilson, Rory$$b3
000153653 7001_ $$aLehne, Benjamin$$b4
000153653 7001_ $$aMishra, Pashupati P$$b5
000153653 7001_ $$aGao, Xu$$b6
000153653 7001_ $$aGhanbari, Mohsen$$b7
000153653 7001_ $$aRueda-Ochoa, Oscar L$$b8
000153653 7001_ $$aJuvinao-Quintero, Diana$$b9
000153653 7001_ $$aLoh, Marie$$b10
000153653 7001_ $$aZhang, Weihua$$b11
000153653 7001_ $$aKooner, Jaspal S$$b12
000153653 7001_ $$aGrabe, Hans J$$b13
000153653 7001_ $$aFelix, Stephan B$$b14
000153653 7001_ $$0P:(DE-He78)c67a12496b8aac150c0eef888d808d46$$aSchöttker, Ben$$b15$$udkfz
000153653 7001_ $$0P:(DE-He78)6a8f87626cb610618a60d742677284cd$$aZhang, Yan$$b16$$udkfz
000153653 7001_ $$aGieger, Christian$$b17
000153653 7001_ $$aMüller-Nurasyid, Martina$$b18
000153653 7001_ $$aHeier, Margit$$b19
000153653 7001_ $$aPeters, Annette$$b20
000153653 7001_ $$aLehtimäki, Terho$$b21
000153653 7001_ $$aTeumer, Alexander$$b22
000153653 7001_ $$0P:(DE-He78)90d5535ff896e70eed81f4a4f6f22ae2$$aBrenner, Hermann$$b23$$udkfz
000153653 7001_ $$aWaldenberger, Melanie$$b24
000153653 7001_ $$aIkram, M Arfan$$b25
000153653 7001_ $$avan Meurs, Joyce B J$$b26
000153653 7001_ $$aFranco, Oscar H$$b27
000153653 7001_ $$00000-0003-2830-6813$$aVoortman, Trudy$$b28
000153653 7001_ $$aChambers, John$$b29
000153653 7001_ $$00000-0003-3713-9762$$aStricker, Bruno H$$b30
000153653 7001_ $$aMuka, Taulant$$b31
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