Association of COX2 −765G>C promoter polymorphism and coronary artery disease in Korean population
- 65 Downloads
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.
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.
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.
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.
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.
KeywordsPolymorphism Homocysteine Coronary artery disease Cyclooxygenase-2
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.
This study had been approved by the Institutional Review Board of CHA Bundang Medical Center.
Informed consent was obtained from all individual participants included in the study.
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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