Are P-glycoprotein (ABCB1/MDR1) and endothelial nitric oxide synthase (eNOS) polymorphisms related to severity of the coronary artery disease?



MDR-1, eNOS, Coronary artery disease, Polymorphism, P-glycoprotein


Background/Aim: Atherosclerotic cardiovascular disease is one of the most common causes of morbidity and mortality in developed countries. Genetic and environmental factors are associated with atherosclerosis development. Some single nucleotide polymorphisms have also been directly related to atherosclerosis, for example, polymorphisms that reduce nitric oxide (NO) levels and/or activity have been linked to atherosclerotic diseases. However, the multidrug resistance gene 1 (MDR-1) polymorphism is related to repeated cardiovascular events. This study aimed to investigate the relationship between MDR-1 and endothelial NO synthase (e-NOS) polymorphism and severe coronary artery disease (CAD). Methods: In total, 90 patients presenting with acute coronary syndrome were included in this cross-sectional study. Patients with at least > 70% stenosis in ≥ 2 coronary vessels were defined as severe CAD (Group 1), while those with this same level of involvement in < 2 vessels were diagnosed with single-vessel disease (Group 2). MDR 3435C-T and eNOS T-786C were determined by polymerase chain reaction (PCR) amplification. Comparison of parametric and nonparametric values between the two groups was performed using the Student’s t- or Mann–Whitney U test. Categorical variables were analyzed using the χ2 test. Risk estimations for the association of severe CAD with the polymorphisms were calculated using odds ratio (OR) and 95% confidence intervals by comparing the genotypic combinations. Results: Baseline demographic parameters were similar in both groups, except for the presence of DM and glucose level. T allele of MDR was 42% and 40% in groups 1 and 2, respectively (OR = 1.12). The C allele of eNOS was 34% and 30% in groups 1 and 2, respectively (OR = 1.16). Fourteen and 15 patients (40% and 27%, respectively) had both T and C alleles in patients in groups 1 and 2, respectively (OR = 1.77). All P-values were > 0.05. Conclusion: This study is the first one that shows that MDR1 and e-NOS polymorphisms are frequent in patients with ≥ 2 vessel disease and may be associated with severe CAD.


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Glagov S, Weisenberg E, Zarins CK, Stankunavicius R, Kolettis GJ. Compensatory enlargement of human atherosclerotic coronary arteries. N Engl J Med. 1987 May 28;316(22):1371-5.

Korkmaz H, Akbulut M, Ozbay Y, Koç M. The relation of intima-media thickness with endothelial function and left ventricular mass index. Anadolu Kardiyol Derg. 2010 Jun;10(3):220-5.

Schmidt HH, Walter U. NO at work. Cell. 1994 Sep 23;78(6):919-25.

Moncada S, Higgs A. The L-arginine-nitric oxide pathway. N Engl J Med. 1993 Dec 30;329(27):2002-12.

Nakayama M, Yasue H, Yoshimura M, Shimasaki Y, Kugiyama K, Ogawa H, et al. T-786-->C mutation in the 5'-flanking region of the endothelial nitric oxide synthase gene is associated with coronary spasm. Circulation. 1999 Jun 8;99(22):2864-70.

Colombo MG, Paradossi U, Andreassi MG, Botto N, Manfredi S, Masetti S, et al. Endothelial Nitric Oxide Synthase Gene Polymorphisms And Risk Of Coronary Artery Disease. Clin Chem. 2003 Mar;49(3):389-95.

Nakayama M, Yasue H, Yoshimura M, Shimasaki Y, Ogawa H, Kugiyama K, et al. T (-786)--> C mutation in the 5'-flanking region of the endothelial nitric oxide synthase gene is associated with myocardial infarction, especially without coronary organic stenosis. Am J Cardiol. 2000 Sep 15;86(6):628-34.

Tangurek B, Ozer N, Sayar N, Terzi S, Yilmaz H, Dayi SU, et al. The relationship between endothelial nitric oxide synthase gene polymorphism (T-786C) and coronary artery disease in the Turkish population. Heart Vessels. 2006 Sep;21(5):285-90.

Sakaeda T. MDR1 genotype-related pharmacokinetics: fact or fiction? Drug Metab Pharmacokinet. 2005 Dec;20(6):391-414.

Mega JL, Close SL, Wiviott SD, Shen L, Walker JR, Simon T, et al. Genetic Variants İn ABCB1 And CYP2C19 And Cardiovascular Outcomes After Treatment with Clopidogrel And Prasugrel in the TRITON-TIMI 38 Trial: A Pharmacogenetic Analysis Lancet. 2010 Oct 16;376(9749):1312-9.

Hamm CW, Bassand JP, Agewall S, Bax J, Boersma E, Bueno H, et al. ESC Committee for Practice Guidelines. ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2011 Dec;32(23):2999-3054.

Steg PG, James SK, Atar D, Badano LP, Blömstrom-Lundqvist C, Borger MA, et al. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J. 2012 Oct;33(20):2569-619.

Rossi GP, Cesari M, Zanchetta M, Colonna S, Maiolino G, Pedon L, et al. The T-786C Endothelial Nitric Oxide Synthase Genotype İs A Novel Risk Factor For Coronary Artery Disease İn Caucasian Patients Of The GENICA Study. J Am Coll Cardiol. 2003 Mar 19;41(6):930-7.

Fatini C, Sofi F, Sticchi E, Gensini F, Gori AM, Fedi S, et al. Influence of endothelial nitric oxide synthase gene polymorphisms (G894T, 4a4b, T-786C) and hyperhomocysteinemia on the predisposition to acute coronary syndromes. Am Heart J. 2004 Mar;147(3):516-21.

Tangürek B, Özer N, Sayar N, Terzi S, Yılmaz HY, Asiltürk R, et al. The relationship between endothelial nitric oxide synthase gene polymorphism (T-786 C) and coronary artery disease in a Turkish population. Turk Kardiyol Dern Ars. 2005; 33(8):467-72.

Uwabo J, Soma M, Nakayama T, Kanmatsuse K. Association of A Variable Number Of Tandem Repeats İn The Endothelial Constitutive Nitric Oxide Synthase Gene With Essential Hypertension İn Japanese. Am J Hypertens. 1998 Jan;11(1 Pt 1):125-8.

Montrucchio G, Alloatti G, Camussi G. Role of platelet-activating factor in cardiovascular pathophysiology. Physiol Rev. 2000 Oct;80(4):1669-99.

Demopoulos CA, Karantonis HC, Antonopoulou S. Platelet activating factor-A molecular link between atherosclerosis theories. Eur J Lipid Sci Technol. 2003 Nov 06;105(11):705-16

Libby P. Inflammation in atherosclerosis. Nature. 2002 Dec 19-26;420(6917):868-74.

Mueller HW, Haught CA, McNatt JM, Cui K, Gaskell SJ, Johnston DA, et al. Measurement of platelet-activating factor in a canine model coronary thrombosis and in endarterectomy samples from patients with advanced coronary artery disease. Circ Res. 1995 Jul;77(1):54-63.

Zheng GH, Xiong SQ, Mei LJ, Chen HY, Wang T, Chu JF. Elevated plasma platelet-activating factor, platelet-activating factor acetylhydrolase levels and risk of coronary heart disease or blood stasis syndrome of coronary heart disease in Chinese: a case-control study. Inflammation. 2012 Aug;35(4):1419-28.

Tao YK, Zhao SP, Yu PL, Shi J, Gu CD, Sun HT, et al. Elevated platelet-activating factor level in ischemia-related arrhythmia and its electrophysiological effect on the myocardium. Biomed Environ Sci. 2013 May;26(5):365-70.

Campa D, Sainz J Pardini B, Vodickova L, Naccarati A, Rudolph A, Novotny J, et al. A comprehensive investigation on common polymorphisms in the MDR1/ABCB1 transporter gene and susceptibility to colorectal cancer. PLoS One. 2012;7(3):e32784.

Ayaz G, Batar B, Kanigur G, Guven M, Onaran I, Karadag B, et al. The association of MDR1 C3435T and G2677T/A polymorphisms with plasma platelet-activating factor levels and coronary artery disease risk in Turkish population. Gene. 2013 Sep 15;527(1):301-5.

Spiewak M, Małek ŁA, Kostrzewa G, et al. Influence of C3435T multidrug resistance gene-1 (MDR-1) polymorphism on platelet reactivity and prognosis in patients with acute coronary syndromes. Kardiol Pol. 2009 Aug;67(8):827-34.






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Öztürk U, Gazi E, Özdemir Öztürk. Are P-glycoprotein (ABCB1/MDR1) and endothelial nitric oxide synthase (eNOS) polymorphisms related to severity of the coronary artery disease?. J Surg Med [Internet]. 2022 Apr. 1 [cited 2022 Sep. 28];6(4):432-5. Available from: