A preliminary study of the association between the ABCA1 gene promoter DNA methylation and coronary artery disease risk

Document Type : Original article

Authors

1 Health Promotion Research Centre, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran

2 Department of Cardiology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran

3 Department of Medical Laboratory Sciences, School of Paramedical Sciences, Zanjan University of Medical Sciences, Zanjan, Iran

Abstract

Coronary artery disease (CAD) is a common health problem in Iranian population. ATP binding cassette transporter A1 (ABCA1) plays central role in the efflux of the cholesterol from peripheral tissues back to liver. Inactivation of ABCA1 by epigenetic change such as DNA methylation may contribute to the development of CAD. The present study investigated the association between promoter DNA methylation status of ABCA1 with the development and severity of CAD. Our study population consisted of 110 angiographically documented CAD patients and 110 controls. The severity of CAD was determined based on the number of stenotic vessels showing more than 50% stenosis. Promoter DNA methylation status of ABCA1 was determined by methylation specific PCR. Lipid profile was determined by routine colorimetric methods. Results showed that the frequency of ABCA1 DNA methylation was significantly higher in CAD group as compared with control group (16.36% vs 5.45%; P=0.015). Also, the methylation frequency of ABCA1 gene was significantly higher in older CAD patients as compared with younger CAD patients (P=0.038). No association was seen between plasma lipid concentration and the promoter DNA methylation status of ABCA1 (P>0.05). Also, the association between the severity of CAD and methylation of ABCA1 gene was not significant (P>0.05). In conclusion the current study indicated ABCA1 DNA methylation as a significant risk factor for development but not severity of CAD. Also, predisposition to the development of CAD by ABCA1 gene DNA methylation was independent of plasma lipid concentration.

Keywords

References

1. Sarrafzadegan N, Sadeghi M, Oveisgharan S, Iranipour R. Incidence of cardiovascular diseases in an Iranian population: the Isfahan Cohort Study. Arch Iran Med 2013;16:138-144.
2. Seidi A, Mirzaahmadi S, Mahmoodi K, Soltanpour MS. The association between NFKB1-94ATTG ins/del and NFKB1A -826C/T genetic variations and coronary artery disease risk. Mol Biol Res Commun 2018;7:17-24.
3. Nelson RH. Hyperlipidemia as a risk factor for cardiovascular disease. Prim Care 2013;40:195-211.
4. Yu XH, Fu YC, Zhang DW, Yin K, Tang CK. Foam cells in atherosclerosis. Clin Chim Acta 2013;424:245-252.
5. Annema W, Tietge UJ. Regulation of reverse cholesterol transport-a comprehensive appraisal of available animal studies. Nutr Metab (Lond) 2012;9:25.
6. Haghpassand M, Bourassa PA, Francone OL, Aiello RJ. Monocyte/macrophage expression of ABCA1 has minimal contribution to plasma HDL levels. J Clin Invest 2001;108:1315-1320.
7. Wang MD, Franklin V, Marcel YL. In vivo reverse cholesterol transport from macrophages lacking ABCA1 expression is impaired. Arterioscler Thromb Vasc Biol 2007;27:1837-1842.
8. Brunham LR, Singaraja RR, Hayden MR. Variations on a gene: rare and common variants in ABCA1 and their impact on HDL cholesterol levels and atherosclerosis. Annu Rev Nutr 2006;26:105-129.
9. Lu Y, Liu Y, Li Y, Zhang H, Yu M, Kanu JS, Qiao Y, Tang Y, Zhen Q, Cheng Y. Association of ATP-binding cassette transporter A1 gene polymorphisms with plasma lipid variability and coronary heart disease risk. Int J Clin Exp Pathol 2015; 8:13441-13449.
10. Puntoni M, Sbrana F, Bigazzi F, Sampietro T. Tangier disease: epidemiology, pathophysiology, and management. Am J Cardiovasc Drugs 2012;12:303-311.
11. Ghaznavi H, Aali E, Soltanpour MS. Association study of the ATP - binding cassette transporter A1 (ABCA1) rs2230806 genetic variation with lipid profile and coronary artery disease risk in an Iranian population. Open Access Maced J Med Sci 2018;6:274-279.
12. Cyrus C, Vatte C, Al-Nafie A, Chathoth S, Al-Ali R, Al-Shehri A, Akhtar MS, Almansori M, Al-Muhanna F, Keating B, Al-Ali A. The impact of common polymorphisms in CETP and ABCA1 genes with the risk of coronary artery disease in Saudi Arabians. Hum Genomics 2016;10:8.
13. Guay SP, Brisson D, Lamarche B, Gaudet D, Bouchard L. Epipolymorphisms within lipoprotein genes contribute independently to plasma lipid levels in familial hypercholest-erolemia. Epigenetics 2014;9:718-729.
14. Guay SP, Brisson D, Munger J, Lamarche B, Gaudet D, Bouchard L. ABCA1 gene promoter DNA methylation is associated with HDL particle profile and coronary artery disease in familial hypercholesterolemia. Epigenetics 2012;7:464-472.
15. Sayols-Baixeras S, Irvin MR, Elosua R, Arnett DK, Aslibekyan SW. Epigenetics of lipid phenotypes. Curr Cardiovasc Risk Rep 2016;10:31.
16. Lim DH, Maher ER. DNA methylation: a form of epigenetic control of gene expression. Obstet Gynecol 2010;12:37-42.
17. Fernández-Sanlés A, Sayols-Baixeras S, Subirana I, Degano IR, Elosua R. Association between DNA methylation and coronary heart disease or other atherosclerotic events: A systematic review. Atherosclerosis 2017;263:325-333.
18. Hai Z, Zuo W. Aberrant DNA methylation in the pathogenesis of atherosclerosis. Clin Chim Acta 2016;456:69-74.
19. Wang X, Collins HL, Ranalletta M, Fuki IV, Billheimer JT, Rothblat GH, Tall AR, Rader DJ. Macrophage ABCA1 and ABCG1, but not SR-BI, promote macrophage reverse cholesterol transport in vivo. J Clin Invest 2007;117:2216-2224.
20. Qi LP, Chen LF, Dang AM, Li LY, Fang Q, Yan XW. Association between the ABCA1-565C/T gene promoter polymorphism and coronary heart disease severity and cholesterol efflux in the Chinese Han population. Genet Test Mol Biomarkers 2015;19:347-352.
21. Guay SP, Légaré C, Houde AA, Mathieu P, Bossé Y, Bouchard L. Acetylsalicylic acid, aging and coronary artery disease are associated with ABCA1 DNA methylation in men. Clin Epigenetics 2014;6:14.
22. Peng P, Wang L, Yang X, Huang X, Ba Y, Chen X, Guo J, Lian J, Zhou J. A preliminary study of the relationship between promoter methylation of the ABCG1, GALNT2 and HMGCR genes and coronary heart disease. PloS one 2014 ;9:e102265.
23. Rowbotham DA, Marshall EA, Vucic EA, Kennett JY, Lam WL, Martinez VD. Epigenetic changes in aging and Age-related disease. J Aging Sci 2015;3:130.
24.Van Eck M, Bos IS, Kaminski WE, Orso E, Rothe G, Twisk J, Böttcher A, Van Amersfoort ES, Christiansen-Weber TA, Fung-Leung WP, Van Berkel TJ. Leukocyte ABCA1 controls susceptibility to atherosclerosis and macrophage recruitment into tissues. Proc Natl Acad Sci USA 2002;99:6298-6303.
25. Kyriakou T, Hodgkinson C, Pontefract DE, Iyengar S, Howell WM, Wong YK, Eriksson P, Ye S. Genotypic effect of the-565C>T polymorphism in the ABCA1 gene promoter on ABCA1 expression and severity of atherosclerosis. Arterioscler Thromb Vasc Biol 2005;25: 418-423.
26. Zeilinger S, Kühnel B, Klopp N, Baurecht H, Kleinschmidt A, Gieger C, Weidinger S, Lattka E, Adamski J, Peters A, Strauch K. Tobacco smoking leads to extensive genome-wide changes in DNA methylation. PLoS One 2013;8:e63812.
27. Steenaard RV, Ligthart S, Stolk L, Peters MJ, van Meurs JB, Uitterlinden AG, Hofman A, Franco OH, Dehghan A. Tobacco smoking is associated with methylation of genes related to coronary artery disease. Clin Epigenetics 2015;7:54.

Files

Share

How to cite

Statistics