Advertisement

Genes & Genomics

, Volume 41, Issue 9, pp 1055–1062 | Cite as

Association of COX2 −765G>C promoter polymorphism and coronary artery disease in Korean population

  • In Jai Kim
  • Sang Hoon Kim
  • Dong Hoon Cha
  • Sang Wook Lim
  • Jae Youn Moon
  • Jung Oh Kim
  • Chang Soo Ryu
  • Han Sung Park
  • Jung Hoon SungEmail author
  • Nam Keun KimEmail author
Research Article

Abstract

Background

Cyclooxygenase-2 (COX2) plays a role in the formation of prostaglandins, which contribute to the inflammation involved in atherosclerosis. However, the role of the COX2 −765G>C polymorphism in susceptibility to coronary artery disease (CAD) is controversial.

Objective

To identify the association between COX2 −765G>C polymorphism with CAD risk in Korean patients. We recruited 622 patients who were diagnosed to have coronary artery disease and 202 controls who did not have history and vascular disease risk factors.

Methods

Using polymerase chain reaction-restriction fragment length polymorphism, the COX2 −765G>C polymorphism was analyzed in 622 Korean patients who received percutaneous coronary intervention and in 202 healthy control subjects.

Results

The GC+CC genotype frequencies of the −765G>C polymorphism were significantly different between the CAD and control groups. The COX2 −765G>C polymorphism showed peculiar associations with CAD according to the presence of hyperlipidemia and plasma folate levels. However, there were no associations between the −765G>C polymorphism and the rates of hypertension, diabetes mellitus, or homocysteine levels.

Conclusion

This study suggests that the COX2 −765G>C polymorphism is a possible genetic determinant for the risk of CAD, and an individual risk factor in Koreans. Thus, further association studies between the COX2 polymorphism and atherosclerotic-related diseases such as cerebrovascular or cardiovascular diseases in other races or ethnicities will be needed.

Keywords

Polymorphism Homocysteine Coronary artery disease Cyclooxygenase-2 

Notes

Acknowledgements

This work was partly supported by the National Research Foundation Grant funded by the Korean Government (NRF-2017R1D1A1B03030110) and partly supported by a grant from the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (HI18C19990200).

Compliance with ethical standards

Conflict of interest

I.J. Kim, S.H. Kim, D.H. Cha, S.W. Lim, J.Y. Moon, J.O. Kim, C.S. Ryu, H.S. Park, J.H. Sung, and N.K. Kim declare that they have no conflict of interest.

Ethical approval

This study had been approved by the Institutional Review Board of CHA Bundang Medical Center.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

13258_2019_835_MOESM1_ESM.docx (15 kb)
Supplementary material 1 (DOCX 14 kb)

References

  1. Adderley SR, Fitzgerald DJ (1999) Oxidative damage of cardiomyocytes is limited by extracellular regulated kinases 1/2-mediated induction of cyclooxygenase-2. J Biol Chem 274:5038–5046CrossRefPubMedGoogle Scholar
  2. Alexander RW (1994) Inflammation and coronary artery disease. N Engl J Med 331:468–469CrossRefPubMedGoogle Scholar
  3. Baker CS, Hall RJ, Evans TJ, Pomerance A, Maclouf J, Creminon C, Yacoub MH, Polak JM (1999) Cyclooxygenase-2 is widely expressed in atherosclerotic lesions affecting native and transplanted human coronary arteries and colocalizes with inducible nitric oxide synthase and nitrotyrosine particularly in macrophages. Arterioscler Thromb Vasc Biol 19:646–655CrossRefPubMedGoogle Scholar
  4. Belton O, Byrne D, Kearney D, Leahy A, Fitzgerald DJ (2000) Cyclooxygenase-1 and -2-dependent prostacyclin formation in patients with atherosclerosis. Circulation 102:840–845CrossRefPubMedGoogle Scholar
  5. Burleigh ME, Babaev VR, Yancey PG, Major AS, McCaleb JL, Oates JA, Morrow JD, Fazio S, Linton MF (2005) Cyclooxygenase-2 promotes early atherosclerotic lesion formation in ApoE-deficient and C57BL/6 mice. J Mol Cell Cardiol 39:443–452CrossRefPubMedGoogle Scholar
  6. Cheng I, Liu X, Plummer SJ, Krumroy LM, Casey G, Witte JS (2007) COX2 genetic variation, NSAIDs, and advanced prostate cancer risk. Br J Cancer 97:557–561CrossRefPubMedPubMedCentralGoogle Scholar
  7. Chiang SL, Chen PH, Lee CH, Ko AM, Lee KW, Lin YC, Ho PS, Tu HP, Wu DC, Shieh TY et al (2008) Up-regulation of inflammatory signalings by areca nut extract and role of cyclooxygenase-2 -1195G > a polymorphism reveal risk of oral cancer. Cancer Res 68:8489–8498CrossRefPubMedGoogle Scholar
  8. Cipollone F, Prontera C, Pini B, Marini M, Fazia M, De Cesare D, Iezzi A, Ucchino S, Boccoli G, Saba V et al (2001) Overexpression of functionally coupled cyclooxygenase-2 and prostaglandin E synthase in symptomatic atherosclerotic plaques as a basis of prostaglandin E(2)-dependent plaque instability. Circulation 104:921–927CrossRefPubMedGoogle Scholar
  9. Cipollone F, Fazia M, Iezzi A, Zucchelli M, Pini B, De Cesare D, Ucchino S, Spigonardo F, Bajocchi G, Bei R et al (2003) Suppression of the functionally coupled cyclooxygenase-2/prostaglandin E synthase as a basis of simvastatin-dependent plaque stabilization in humans. Circulation 107:1479–1485CrossRefPubMedGoogle Scholar
  10. Cipollone F, Toniato E, Martinotti S, Fazia M, Iezzi A, Cuccurullo C, Pini B, Ursi S, Vitullo G, Averna M et al (2004) A polymorphism in the cyclooxygenase 2 gene as an inherited protective factor against myocardial infarction and stroke. JAMA 291:2221–2228CrossRefPubMedGoogle Scholar
  11. Colaizzo D, Fofi L, Tiscia G, Guglielmi R, Cocomazzi N, Prencipe M, Margaglione M, Toni D (2006) The COX-2 G/C -765 polymorphism may modulate the occurrence of cerebrovascular ischemia. Blood Coagul Fibrinolysis 17:93–96CrossRefPubMedGoogle Scholar
  12. Gao J, Ke Q, Ma HX, Wang Y, Zhou Y, Hu ZB, Zhai XJ, Wang XC, Qing JW, Chen WS et al (2007) Functional polymorphisms in the cyclooxygenase 2 (COX-2) gene and risk of breast cancer in a Chinese population. J Toxicol Environ Health A 70:908–915CrossRefPubMedGoogle Scholar
  13. Hamajima N, Takezaki T, Matsuo K, Saito T, Inoue M, Hirai T, Kato T, Ozeki J, Tajima K (2001) Genotype Frequencies of Cyclooxygenease 2 (COX2) Rare Polymorphisms for Japanese with and without Colorectal Cancer. Asian Pac J Cancer Prev 2:57–62PubMedGoogle Scholar
  14. Hegener HH, Diehl KA, Kurth T, Gaziano JM, Ridker PM, Zee RY (2006) Polymorphisms of prostaglandin-endoperoxide synthase 2 gene, and prostaglandin-E receptor 2 gene, C-reactive protein concentrations and risk of atherothrombosis: a nested case-control approach. J Thromb Haemost 4:1718–1722CrossRefPubMedGoogle Scholar
  15. Hoff JH, te Morsche RH, Roelofs HM, van der Logt EM, Nagengast FM, Peters WH (2009) COX-2 polymorphisms − 765G– > C and -1195A– > G and colorectal cancer risk. World J Gastroenterol 15:4561–4565CrossRefPubMedPubMedCentralGoogle Scholar
  16. Hou L, Grillo P, Zhu ZZ, Lissowska J, Yeager M, Zatonski W, Zhu G, Baccarelli A, Chanock SJ, Fraumeni JF Jr et al (2007) COX1 and COX2 polymorphisms and gastric cancer risk in a Polish population. Anticancer Res 27:4243–4247PubMedGoogle Scholar
  17. Huuskonen KH, Kunnas TA, Tanner MM, Mikkelsson J, Ilveskoski E, Karhunen PJ, Karhunen PJ, Nikkari ST (2008) COX-2 gene promoter polymorphism and coronary artery disease in middle-aged men: the Helsinki sudden death study. Mediat Inflamm 2008:289453CrossRefGoogle Scholar
  18. Ke-Xiang Z, Yu-Min L, Xun L, Wen-Ce Z, Yong S, Tao L (2011) Study on the association of COX-2 genetic polymorphisms with risk of gastric cancer in high incidence Hexi area of Gansu province in China. Mol Biol Rep 38:649–655CrossRefPubMedGoogle Scholar
  19. Koh WP, Yuan JM, van den Berg D, Lee HP, Yu MC (2004) Interaction between cyclooxygenase-2 gene polymorphism and dietary n-6 polyunsaturated fatty acids on colon cancer risk: the Singapore Chinese Health Study. Br J Cancer 90:1760–1764CrossRefPubMedPubMedCentralGoogle Scholar
  20. Kohsaka S, Volcik KA, Folsom AR, Wu KK, Ballantyne CM, Willerson JT, Boerwinkle E (2008) Increased risk of incident stroke associated with the cyclooxygenase 2 (COX-2) G-765C polymorphism in African–Americans: the Atherosclerosis Risk in Communities Study. Atherosclerosis 196:926–930CrossRefPubMedGoogle Scholar
  21. Lee CR, North KE, Bray MS, Couper DJ, Heiss G, Zeldin DC (2008) Cyclooxygenase polymorphisms and risk of cardiovascular events: the Atherosclerosis Risk in Communities (ARIC) study. Clin Pharmacol Ther 83:52–60CrossRefPubMedGoogle Scholar
  22. Li W, Xu J, Wang X, Chen J, Zhang C, Sun K, Hui R (2009) Cyclooxygenase-2 (COX-2) G-765C is a protective factor for coronary artery disease but not for ischemic stroke: a meta-analysis. Atherosclerosis 207:492–495CrossRefPubMedGoogle Scholar
  23. Orbe J, Beloqui O, Rodriguez JA, Belzunce MS, Roncal C, Paramo JA (2006) Protective effect of the G-765C COX-2 polymorphism on subclinical atherosclerosis and inflammatory markers in asymptomatic subjects with cardiovascular risk factors. Clin Chim Acta 368:138–143CrossRefPubMedGoogle Scholar
  24. Papafili A, Hill MR, Brull DJ, McAnulty RJ, Marshall RP, Humphries SE, Laurent GJ (2002) Common promoter variant in cyclooxygenase-2 represses gene expression: evidence of role in acute-phase inflammatory response. Arterioscler Thromb Vasc Biol 22:1631–1636CrossRefPubMedGoogle Scholar
  25. Pereira C, Sousa H, Ferreira P, Fragoso M, Moreira-Dias L, Lopes C, Medeiros R, Dinis-Ribeiro M (2006) 765G>C COX-2 polymorphism may be a susceptibility marker for gastric adenocarcinoma in patients with atrophy or intestinal metaplasia. World J Gastroenterol 12:5473–5478CrossRefPubMedPubMedCentralGoogle Scholar
  26. Ryu CS, Sakong JH, Ahn EH, Kim JO, Ko D, Kim JH, Lee WS, Kim NK (2019) Association study of the three functional polymorphisms (TAS2R46G > A, OR4C16G > A, and OR4X1A > T) with recurrent pregnancy loss. Genes Genom 41:61–70CrossRefGoogle Scholar
  27. Santovito D, Mezzetti A, Cipollone F (2009) Cyclooxygenase and prostaglandin synthases: roles in plaque stability and instability in humans. Curr Opin Lipidol 20:402–408CrossRefPubMedGoogle Scholar
  28. Schönbeck U, Sukhova GK, Graber P, Coulter S, Libby P (1999) Augmented expression of cyclooxygenase-2 in human atherosclerotic lesions. Am J Pathol 155:1281–1291CrossRefPubMedPubMedCentralGoogle Scholar
  29. Shinmura K, Tang XL, Wang Y, Xuan YT, Liu SQ, Takano H, Bhatnagar A, Bolli R (2000) Cyclooxygenase-2 mediates the cardioprotective effects of the late phase of ischemic preconditioning in conscious rabbits. Proc Natl Acad Sci USA 97:10197–10202CrossRefPubMedGoogle Scholar
  30. Smith WL, Langenbach R (2001) Why there are two cyclooxygenase isozymes. J Clin Invest 107:1491–1495CrossRefPubMedPubMedCentralGoogle Scholar
  31. Tan W, Wu J, Zhang X, Guo Y, Liu J, Sun T, Zhang B, Zhao D, Yang M, Yu D et al (2007) Associations of functional polymorphisms in cyclooxygenase-2 and platelet 12-lipoxygenase with risk of occurrence and advanced disease status of colorectal cancer. Carcinogenesis 28:1197–1201CrossRefPubMedGoogle Scholar
  32. Tanabe T, Tohnai N (2002) Cyclooxygenase isozymes and their gene structures and expression. Prostaglandins Other Lipid Mediat 68–69:95–114CrossRefPubMedGoogle Scholar
  33. Upadhyay R, Jain M, Kumar S, Ghoshal UC, Mittal B (2009) Functional polymorphisms of cyclooxygenase-2 (COX-2) gene and risk for esophageal squmaous cell carcinoma. Mutat Res 663:52–59CrossRefPubMedGoogle Scholar
  34. Vane SJ (1998) Differential inhibition of cyclooxygenase isoforms: an explanation of the action of NSAIDs. J Clin Rheumatol 4:s3–10CrossRefPubMedGoogle Scholar
  35. Xie X, Ma YT (2009) Postacyclin synthase cyclooxygenase-2 gene polymorphism is associated with myocardial infarction in Xinjiang Uygur population study. Website Xinjiang Medical University Website. http://zhlxbxzz.yiigle.com/CN112338200806/592565.htm?locale=zh_CN. Accessed 05 Sept 2018
  36. Xie X, Ma YT, Fu ZY, Yang YN, Wang YH, Chen BD, Liu F (2008) Study on the association of cyclooxygenase-2 -765 G>C and prostacyclin synthase C1117A polymorphisms and the risk of myocardial infarction in Uigur population of Xinjiang, China. Zhonghua Liu Xing Bing Xue Za Zhi 29:598–603PubMedGoogle Scholar
  37. Xie X, Ma YT, Fu ZY, Yang YN, Ma X, Chen BD, Wang YH, Liu F (2009) Association of polymorphisms of PTGS2 and CYP8A1 with myocardial infarction. Clin Chem Lab Med 47:347–352CrossRefPubMedGoogle Scholar
  38. Xie X, Ma YT, Yang YN, Fu ZY, Li XM, Huang D, Ma X, Chen BD, Liu F (2011) Interaction between COX-2 G-765C and smoking in relation to coronary artery disease in a Chinese Uighur population. Clin Chem Lab Med 49:55–60PubMedGoogle Scholar
  39. Xing LL, Wang ZN, Jiang L, Zhang Y, Xu YY, Li J, Luo Y, Zhang X (2008) Cyclooxygenase 2 polymorphism and colorectal cancer: − 765G>C variant modifies risk associated with smoking and body mass index. World J Gastroenterol 14:1785–1789CrossRefPubMedPubMedCentralGoogle Scholar
  40. Yang H, Gu J, Lin X, Grossman HB, Ye Y, Dinney CP, Wu X (2008) Profiling of genetic variations in inflammation pathway genes in relation to bladder cancer predisposition. Clin Cancer Res 14:2236–2244CrossRefPubMedGoogle Scholar
  41. Zhang X, Miao X, Tan W, Ning B, Liu Z, Hong Y, Song W, Guo Y, Zhang X, Shen Y et al (2005) Identification of functional genetic variants in cyclooxygenase-2 and their association with risk of esophageal cancer. Gastroenterology 129:565–576PubMedGoogle Scholar
  42. Zhao D, Xu D, Zhang X, Wang L, Tan W, Guo Y, Yu D, Li H, Zhao P, Lin D (2009) Interaction of cyclooxygenase-2 variants and smoking in pancreatic cancer: a possible role of nucleophosmin. Gastroenterology 136:1659–1668CrossRefPubMedGoogle Scholar

Copyright information

© The Genetics Society of Korea 2019

Authors and Affiliations

  • In Jai Kim
    • 1
    • 2
  • Sang Hoon Kim
    • 1
  • Dong Hoon Cha
    • 1
  • Sang Wook Lim
    • 1
  • Jae Youn Moon
    • 1
  • Jung Oh Kim
    • 2
  • Chang Soo Ryu
    • 2
  • Han Sung Park
    • 2
  • Jung Hoon Sung
    • 1
    Email author
  • Nam Keun Kim
    • 2
    Email author
  1. 1.Department of Cardiology, CHA Bundang Medical Center, School of MedicineCHA UniversitySeongnamSouth Korea
  2. 2.Department of Biomedical Science, College of Life ScienceCHA UniversitySeongnamSouth Korea

Personalised recommendations