Korean Circulation Journal

The Korean Society of Cardiology (대한심장학회)
권호 표지
DOI QR코드

DOI QR Code

Association of rs10757274 and rs2383206 Polymorphisms on 9p21 locus with Coronary Artery Disease in Turkish Population

  • Yayla, Cagri (Department of Cardiology, School of Medicine, Gazi University) ;
  • Okyay, Kaan (Department of Cardiology, School of Medicine, Baskent University) ;
  • Yilmaz, Akin (Department of Medical Biology and Genetic, School of Medicine, Gazi University) ;
  • Sahinarslan, Asife (Department of Cardiology, School of Medicine, Gazi University) ;
  • Yar Saglam, Atiye Seda (Department of Medical Biology and Genetic, School of Medicine, Gazi University) ;
  • Eyiol, Azmi (Department of Cardiology, School of Medicine, Gazi University) ;
  • Bolayir, Hasan Ata (Department of Cardiology, School of Medicine, Gazi University) ;
  • Sezenoz, Burak (Department of Cardiology, School of Medicine, Gazi University) ;
  • Menevse, Sevda (Department of Medical Biology and Genetic, School of Medicine, Gazi University) ;
  • Cengel, Atiye (Department of Cardiology, School of Medicine, Gazi University)
  • Received : 2015.09.06
  • Accepted : 2015.12.11
  • Published : 2016.09.30
⟨ Previous Next ⟩

Abstract

Background and Objectives: Genetic predisposition is an important risk factor for coronary artery disease (CAD). In this study, we aimed to evaluate the impact of rs10757274 and rs2383206 polymorphisms in chromosome 9p21 on presence and severity of CAD in a Turkish population. Subjects and Methods: A total of 646 patients who underwent coronary angiography were included in this study. Coronary vessel score and Gensini score were calculated to assess the angiographic severity of CAD. Alleles of AA, AG, and GG were determined for rs10757274 (polymorphism-1) and rs2383206 (polymorphism-2) polymorphisms located in chromosome 9p21 from the blood samples. Results: There was a significant difference between the alleles in polymorphism-1 in the presence of coronary artery disease (38.9% in AA, 48.0% in GG and 56.4% in AG, p=0.017). However, there was no difference between the alleles in polymorphism-2. According to vessel scores, there was a significant difference between the alleles in polymorphism-1 (AA $0.71{\pm}1.04$, GG $0.88{\pm}1.07$, AG $1.06{\pm}1.12$, p=0.018). In polymorphism-2, vessel scores did not show a difference between the alleles. In polymorphism-1, there was a significant difference in Gensini score (p=0.041). Gensini scores did not differ between the alleles in polymorphism-2 (p>0.05 for all). In multivariate analyses, none of the alleles was an independent factor for presence of CAD. Conclusion: The presence of rs10757274 polymorphism including AG allele in chromosome 9p21 was related to CAD. However, this relationship was not independent of other cardiovascular risk factors.

Keywords

References

  1. Okrainec K, Banerjee DK, Eisenberg MJ. Coronary artery disease in the developing world. Am Heart J 2004;148:7-15. https://doi.org/10.1016/j.ahj.2003.11.027
  2. Ahn SG, Yoon J, Kim J, et al. genotype- and phenotype-directed personalization of antiplatelet treatment in patients with non-ST elevation acute coronary syndromes undergoing coronary stenting. Korean Circ J 2013;43:541-9. https://doi.org/10.4070/kcj.2013.43.8.541
  3. Shin DJ, Lee SH, Park S, Jang Y. Association between serine/threonine kinase 39 gene polymorphism, hypertension, and other cardiovascular risk factors in Koreans. Korean Circ J 2013;43:13-22. https://doi.org/10.4070/kcj.2013.43.1.13
  4. Yoo SY, Kim J, Cheong S, et al. Rho-associated kinase 2 polymorphism in patients with vasospastic angina. Korean Circ J 2012;42:406-13. https://doi.org/10.4070/kcj.2012.42.6.406
  5. Chan L, Boerwinkle E. Gene-environment interactions and gene therapy in atherosclerosis. Cardiol Rev 1994;2:130-7. https://doi.org/10.1097/00045415-199405000-00003
  6. Roberts R, Stewart AF. Genes and coronary artery disease: where are we? J Am Coll Cardiol 2012;60:1715-21. https://doi.org/10.1016/j.jacc.2011.12.062
  7. McPherson R, Pertsemlidis A, Kavaslar N, et al. A common allele on chromosome 9 associated with coronary heart disease. Science 2007;316:1488-91. https://doi.org/10.1126/science.1142447
  8. Helgadottir A, Thorleifsson G, Manolescu A, et al. A common variant on chromosome 9p21 affects the risk of myocardial infarction. Science 2007;316:1491-3. https://doi.org/10.1126/science.1142842
  9. Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 2007;447:661-78. https://doi.org/10.1038/nature05911
  10. Ding H, Xu Y, Wang X, et al. 9p21 is a shared susceptibility locus strongly for coronary artery disease and weakly for ischemic stroke in Chinese Han population. Circ Cardiovasc Genet 2009;2:338-46. https://doi.org/10.1161/CIRCGENETICS.108.810226
  11. Hinohara K, Nakajima T, Takahashi M, et al. Replication of the association between a chromosome 9p21 polymorphism and coronary artery disease in Japanese and Korean populations. J Hum Genet 2008;53:357-9. https://doi.org/10.1007/s10038-008-0248-4
  12. Saleheen D, Alexander M, Rasheed A, et al. Association of the 9p21.3 locus with risk of first-ever myocardial infarction in Pakistanis: casecontrol study in South Asia and updated meta-analysis of Europeans. Arterioscler Thromb Vasc Biol 2010;30:1467-73. https://doi.org/10.1161/ATVBAHA.109.197210
  13. Kumar J, Yumnam S, Basu T, et al. Association of polymorphisms in 9p21 region with CAD in North Indian population: replication of SNPs identified through GWAS. Clin Genet 2011;79:588-93. https://doi.org/10.1111/j.1399-0004.2010.01509.x
  14. Palomaki GE, Melillo S, Bradley LA. Association between 9p21 genomic markers and heart disease: a meta-analysis. JAMA 2010;303:648-56. https://doi.org/10.1001/jama.2010.118
  15. Helgadottir A, Thorleifsson G, Magnusson KP, et al. The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm. Nat Genet 2008;40:217-24. https://doi.org/10.1038/ng.72
  16. Emanuele E, Lista S, Ghidoni R, et al. Chromosome 9p21.3 genotype is associated with vascular dementia and Alzheimer's disease. Neurobiol Aging 2011;32:1231-5. https://doi.org/10.1016/j.neurobiolaging.2009.07.003
  17. Kral BG, Mathias RA, Suktitipat B, et al. A common variant in the CDKN2B gene on chromosome 9p21 protects against coronary artery disease in Americans of African ancestry. J Hum Genet 2011;56:224-9. https://doi.org/10.1038/jhg.2010.171
  18. Munir MS, Wang Z, Alahdab F, et al. The association of 9p21-3 locus with coronary atherosclerosis: a systematic review and metaanalysis. BMC Med Genet 2014;15:66.
  19. Gensini GG. A more meaningful scoring system for determining the severity of coronary heart disease. Am J Cardiol 1983;51:606. https://doi.org/10.1016/S0002-9149(83)80105-2
  20. Yusuf S, Hawken S, Ounpuu S, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet 2004;364:937-52. https://doi.org/10.1016/S0140-6736(04)17018-9
  21. Di Chiara A, Vanuzzo D. Does surveillance impact on cardiovascular prevention? Eur Heart J 2009;30:1027-9. https://doi.org/10.1093/eurheartj/ehp025
  22. CARDIoGRAMplusC4D Consortium, Deloukas P, Kanoni S, et al. Large-scale association analysis identifies new risk loci for coronary artery disease. Nat Genet 2013;45:25-33. https://doi.org/10.1038/ng.2480
  23. Franceschini N, Carty C, Buzkova P, et al. Association of genetic variants and incident coronary heart disease in multiethnic cohorts: the PAGE study. Circ Cardiovasc Genet 2011;4:661-72. https://doi.org/10.1161/CIRCGENETICS.111.960096
  24. Dandona S, Stewart AF, Chen L, et al. Gene dosage of the common variant 9p21 predicts severity of coronary artery disease. J Am Coll Cardiol 2010;56:479-86. https://doi.org/10.1016/j.jacc.2009.10.092
  25. Congrains A, Kamide K, Oguro R, et al. Genetic variants at the 9p21 locus contribute to atherosclerosis through modulation of ANRIL and CDKN2A/B. Atherosclerosis 2012;220:449-55. https://doi.org/10.1016/j.atherosclerosis.2011.11.017
  26. Yap KL, Li S, Munoz-Cabello AM, et al. Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a. Mol Cell 2010;38:662-74. https://doi.org/10.1016/j.molcel.2010.03.021
  27. Vijayachandra K, Higgins W, Lee J, Glick A. Induction of p16ink4a and p19ARF by TGFbeta1 contributes to growth arrest and senescence response in mouse keratinocytes. Mol Carcinog 2009;48:181-6. https://doi.org/10.1002/mc.20472
  28. Chen HH, Almontashiri NA, Antoine D, Stewart AF. Functional genomics of the 9p21.3 locus for atherosclerosis: clarity or confusion? Curr Cardiol Rep 2014;16:502. https://doi.org/10.1007/s11886-014-0502-7
  29. Cakmak HA, Bayoglu B, Durmaz E, et al. Evaluation of association between common genetic variants on chromosome 9p21 and coronary artery disease in Turkish population. Anatol J Cardiol 2015;15:196-203. https://doi.org/10.5152/akd.2014.5285
  30. Onat A, Ugur M, Cicek G, et al. The Turkish Adult Risk Factor survey 2009: similar cardiovascular mortality in rural and urban areas. Turk Kardiyol Dern Ars 2010;38:159-63.

Cited by

  1. Genome-Wide Association Studies in Patients With Coronary Artery Disease vol.73, pp.1, 2016, https://doi.org/10.1177/00033197211022076