Statin Use Associates With Risk of Type 2 Diabetes via Epigenetic Patterns atABCG1

被引：12
作者：
Liu, Yuwei [1 ,2 ]
Shen, Yu [2 ]
Guo, Tao [2 ,3 ]
Parnell, Laurence D. [4 ]
Westerman, Kenneth E. [2 ]
Smith, Caren E. [2 ]
Ordovas, Jose M. [2 ,5 ,6 ]
Lai, Chao-Qiang [4 ]
机构：
[1] Fudan Univ, Sch Publ Hlth, Shanghai, Peoples R China
[2] Tufts Univ, JM USDA Human Nutr Res Ctr Aging, Nutr & Genom Lab, Boston, MA 02111 USA
[3] Wuhan Univ, Zhongnan Hosp, Dept Cardiol, Wuhan, Peoples R China
[4] Tufts Univ, USDA ARS, Nutr & Genom Lab, JM USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA
[5] CEI UAM CSIC, IMDEA Food Inst, Madrid, Spain
[6] Ctr Nacl Invest Cardiovasc CNIC, Madrid, Spain
来源：
FRONTIERS IN GENETICS | 2020年 / 11卷
基金：
美国国家卫生研究院;
关键词：
statin; ABCG1; methylation; type; 2; diabetes; cg06500161; EPIGENOME-WIDE ASSOCIATION; DNA METHYLATION; CAUSAL ROLE; ABCG1; INSULIN; GLUCOSE; BLOOD; ABCA1; AGE; TRANSPORTER;
D O I：
10.3389/fgene.2020.00622
中图分类号：
Q3 [遗传学];
学科分类号：
071007 ; 090102 ;
摘要：
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 ofABCG1through which statin use associates with risk of type 2 diabetes. We determined the association between the statin use, DNA methylation atABCG1and 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 ofABCG1and biological pathways on the pathogenesis of type 2 diabetes. Our results showed that DNA methylation levels at cg06500161 ofABCG1were 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 ofABCG1, ABCA1andACSL3, 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 atABCG1is a mediator of the association between statins and risk of type 2 diabetes.
引用
收藏
页数：11
相关论文
共 50 条
[1]  
Aguirre L, 2013, J PHYSIOL PHARMACOL, V64, P281
[2]  
Anderson G, 1998, CONTROL CLIN TRIALS, V19, P61
[3]   Characterization of Acyl-CoA synthetase isoforms in pancreatic beta cells: Gene silencing shows participation of ACSL3 and ACSL4 in insulin secretion [J].
Ansari, Israr-Ul H. ;
Longacre, Melissa J. ;
Stoker, Scott W. ;
Kendrick, Mindy A. ;
O'Neill, Lucas M. ;
Zitur, Laura J. ;
Fernandez, Luis A. ;
Ntambi, James M. ;
MacDonald, Michael J. .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 2017, 618 :32-43
[4]   Epigenome-wide association study (EWAS) on lipids: the Rotterdam Study [J].
Braun, Kim V. E. ;
Dhana, Klodian ;
de Vries, Paul S. ;
Voortman, Trudy ;
van Meurs, Joyce B. J. ;
Uitterlinden, Andre G. ;
Hofman, Albert ;
Hu, Frank B. ;
Franco, Oscar H. ;
Dehghan, Abbas .
CLINICAL EPIGENETICS, 2017, 9
[5]   Epigenetic alterations in blood mirror age-associated DNA methylation and gene expression changes in human liver [J].
Bysani, Madhusudhan ;
Perfilyev, Alexander ;
de Mello, Vanessa D. ;
Ronn, Tina ;
Nilsson, Emma ;
Pihlajamaki, Jussi ;
Ling, Charlotte .
EPIGENOMICS, 2017, 9 (02) :105-122
[6]   Exploring a causal role of DNA methylation in the relationship between maternal vitamin B12 during pregnancy and child's IQ at age 8, cognitive performance and educational attainment: a two-step Mendelian randomization study [J].
Caramaschi, Doretta ;
Sharp, Gemma C. ;
Nohr, Ellen A. ;
Berryman, Katie ;
Lewis, Sarah J. ;
Smith, George Davey ;
Relton, Caroline L. .
HUMAN MOLECULAR GENETICS, 2017, 26 (15) :3001-3013
[7]   Epigenome-wide association of DNA methylation markers in peripheral blood from Indian Asians and Europeans with incident type 2 diabetes: a nested case-control study [J].
Chambers, John C. ;
Loh, Marie ;
Lehne, Benjamin ;
Drong, Alexander ;
Kriebel, Jennifer ;
Motta, Valeria ;
Wahl, Simone ;
Elliott, Hannah R. ;
Rota, Federica ;
Scott, William R. ;
Zhang, Weihua ;
Tan, Sian-Tsung ;
Campanella, Gianluca ;
Chadeau-Hyam, Marc ;
Yengo, Loic ;
Richmond, Rebecca C. ;
Adamowicz-Brice, Martyna ;
Afzal, Uzma ;
Bozaoglu, Kiymet ;
Mok, Zuan Yu ;
Ng, Hong Kiat ;
Pattou, Francois ;
Prokisch, Holger ;
Rozario, Michelle Ann ;
Tarantini, Letizia ;
Abbott, James ;
Ala-Korpela, Mika ;
Albetti, Benedetta ;
Ammerpohl, Ole ;
Bertazzi, Pier Alberto ;
Blancher, Christine ;
Caiazzo, Robert ;
Danesh, John ;
Gaunt, Tom R. ;
de Lusignan, Simon ;
Gieger, Christian ;
Illig, Thomas ;
Jha, Sujeet ;
Jones, Simon ;
Jowett, Jeremy ;
Kangas, Antti J. ;
Kasturiratne, Anuradhani ;
Kato, Norihiro ;
Kotea, Navaratnam ;
Kowlessur, Sudhir ;
Pitkaeniemi, Janne ;
Punjabi, Prakash ;
Saleheen, Danish ;
Schafmayer, Clemens ;
Soininen, Pasi .
LANCET DIABETES & ENDOCRINOLOGY, 2015, 3 (07) :526-534
[8]   Second-generation PLINK: rising to the challenge of larger and richer datasets [J].
Chang, Christopher C. ;
Chow, Carson C. ;
Tellier, Laurent C. A. M. ;
Vattikuti, Shashaank ;
Purcell, Shaun M. ;
Lee, James J. .
GIGASCIENCE, 2015, 4
[9]   Statins for Prevention of Cardiovascular Disease in Adults Evidence Report and Systematic Review for the US Preventive Services Task Force [J].
Chou, Roger ;
Dana, Tracy ;
Blazina, Ian ;
Daeges, Monica ;
Jeanne, Thomas L. .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2016, 316 (19) :2008-2024
[10]   DNA methylation map in circulating leukocytes mirrors subcutaneous adipose tissue methylation pattern: a genome-wide analysis from non-obese and obese patients [J].
Crujeiras, A. B. ;
Diaz-Lagares, A. ;
Sandoval, J. ;
Milagro, F. I. ;
Navas-Carretero, S. ;
Carreira, M. C. ;
Gomez, A. ;
Hervas, D. ;
Monteiro, M. P. ;
Casanueva, F. F. ;
Esteller, M. ;
Martinez, J. A. .
SCIENTIFIC REPORTS, 2017, 7
12345