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23.10.2020 | Original articles

Genetic association between eNOS gene polymorphisms and risk of carotid atherosclerosis

A meta-analysis

verfasst von: Yongheng Chen, Lin Chen, Qiliang Zhou

Erschienen in: Herz | Sonderheft 2/2021

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Abstract

Background

Endothelial nitric oxide synthase (eNOS) has been reported to be involved in the atherosclerotic process. A number of studies have investigated the association between eNOS gene polymorphisms and the risk of carotid atherosclerosis (CAS). However, the results are conflicting and inconclusive. The aim of this study was to evaluate precisely the association between the eNOS T786C, G894T, and 4a/4b polymorphisms and CAS risk.

Material and methods

A meta-analysis was carried out by retrieving relevant studies from PubMed, Embase, China National Knowledge Infrastructure (CNKI), and Cochrane databases without a restriction on publication year. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to describe the strength of the association with CAS.

Results

Data were obtained from eight case-control studies comprising 2975 cases and 2624 controls. Significant associations were detected between the allelic and recessive models of the eNOS T786C polymorphism (allelic: p = 0.04; OR, 95% CI = 1.57 [1.01, 2.44]; recessive: p = 0.03; OR, 95% CI = 1.53 [1.04, 2.24]), as well as the allelic and dominant models of the eNOS 4a/4b polymorphism, and CAS risk in an Asian subgroup (allelic: p = 0.02; OR, 95% CI = 1.49 [1.07, 2.07]; dominant: p = 0.01; OR, 95% CI = 1.50 [1.09, 2.05]), but not in a Caucasian subgroup (p > 0.05). No association was observed between the eNOS G894T polymorphism and CAS risk (p > 0.05).

Conclusion

Our study provides evidence that the allelic and recessive models of the eNOS T786C polymorphism and the allelic and dominant models of the eNOS 4a/4b polymorphism may increase the risk of CAS in Asian populations.

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Leblanc S, Bibeau K, Bertrand OF, Lévesque V, Deschênes St-Pierre B et al (2017) Carotid versus coronary atherosclerosis burdens in acute compared with chronic symptomatic coronary artery disease. Can J Physiol Pharmacol 95(8):878–887PubMedCrossRef

Sugioka K, Naruko T, Matsumura Y, Shirai N, Hozumi T, Yoshiyama M et al (2010) Neopterin and atherosclerotic plaque instability in coronary and carotid arteries. J Atheroscler Thromb 17(11):1115–1121PubMedCrossRef

Nakashima Y, Fujii H, Sumiyoshi S, Wight TN, Sueishi K (2007) Accumulation of lipid and proteoglycans in intimal thickenings followed by macrophage infiltration. Early human atherosclerosis. Arterioscler Thromb Vasc Biol 27(5):1159–1165PubMedCrossRef

Kim HY, Kim CJ, Rho TH, Youn HJ, Jin SW, Rhim HY et al (1999) Transesophageal echocardiographic detection of thoracic aortic plaque could noninvasively predict significant obstructive coronary artery disease. Korean J Intern Med 14(2):20–26PubMedPubMedCentralCrossRef

Yamasaki Y, Kodama M, Nishizawa H, Sakamoto K, Matsuhisa M, Kajimoto Y et al (2000) Carotid intima-media thickness in Japanese type 2 diabetic subjects: predictors of progression and relationship with incident coronary heart disease. Diabetes Care 23(9):1310–1315PubMedCrossRef

Hamrah MS, Suzuki S, Ishii H, Shibata Y, Tatami Y, Osugi N et al (2015) Impact of airflow limitation on carotid atherosclerosis in coronary artery disease patients. Respiration 89(4):322–328PubMedCrossRef

Jander S, Stegemann E (2014) Carotid atherosclerosis in coronary heart disease. Dtsch Med Wochenschr 139(23):1224–1227PubMedCrossRef

Jashari F, Ibrahimi P, Nicoll R, Bajraktari G, Wester P, Henein MY (2013) Coronary and carotid atherosclerosis: similarities and differences. Atherosclerosis 227(2):193–200PubMedCrossRef

Omisore AD, Famurewa OC, Komolafe MA, Asaleye CM, Fawale MB, Afolabi BI (2018) Association of traditional cardiovascular risk factors with carotid atherosclerosis among adults at a teaching hospital in south-western Nigeria. Cardiovasc J Afr 29:1–7CrossRef

10.

Bonora E, Kiechl S, Oberhollenzer F, Egger G, Bonadonna RC, Muggeo M et al (2000) Impaired glucose tolerance, Type II diabetes mellitus and carotid atherosclerosis: prospective results from the Bruneck Study. Diabetologia 43(2):156–164PubMedCrossRef

11.

Corrado E, Rizzo M, Muratori I, Coppola G, Novo S (2006) Association of elevated fibrinogen and c‑reactive protein levels with carotid lesions in patients with newly diagnosed hypertension or type ii diabetes. Arch Med Res 37(8):1004–1009PubMedCrossRef

12.

Cuomo S, Guarini P, Gaeta G, De MM, Boeri F, Dorn J (2002) Increased carotid intima-media thickness in children-adolescents, and young adults with a parental history of premature myocardial infarction. Eur Heart J 23(17):1345–1350PubMedCrossRef

13.

Reschen ME, Lin D, Chalisey A, Soilleux EJ, O’Callaghan CA (2016) Genetic and environmental risk factors for atherosclerosis regulate transcription of phosphatase and actin regulating gene PHACTR1. Atherosclerosis 250:95–105PubMedPubMedCentralCrossRef

14.

Org E, Mehrabian M, Lusis AJ (2015) Unraveling the environmental and genetic interactions in atherosclerosis: central role of the gut microbiota. Atherosclerosis 241(2):387–399PubMedPubMedCentralCrossRef

15.

Berg K (1984) Twin studies of coronary heart disease and its risk factors. Acta Genet Med Gemellol 33:349–361PubMedCrossRef

16.

Chamberlain JG, Galton DJ (1990) Genetic susceptibility to atherosclerosis. Br Med Bull 46:917–940PubMedCrossRef

17.

Çoban N, Güçlü Geyik F, Yıldırım Ö, Erginel Ünaltuna N (2017) Investigating the role of ceramide metabolism-associated CERS5 (LASS5) gene in atherosclerosis pathogenesis in endothelial cells. Turk Kardiyol Dern Ars 45(2):118–125PubMed

18.

Xie X, Shi X, Liu M (2017) The roles of TLR gene polymorphisms in atherosclerosis: a systematic review and meta-analysis of 35,317 subjects. Scand J Immunol 86(1):50–58PubMedCrossRef

19.

Djordjevic A, Zivkovic M, Stankovic A, Zivotic I, Koncar I, Davidovic L et al (2016) Genetic variants in the vicinity of LGALS‑3 gene and LGALS‑3 mRNA expression in advanced carotid atherosclerosis: an exploratory study. J Clin Lab Anal 30(6):1150–1157PubMedPubMedCentralCrossRef

20.

Thibeault S, Rautureau Y, Oubaha M, Faubert D, Wilkes BC et al (2010) S‑nitrosylation of beta-catenin by eNOS-derived NO promotes VEGF-induced endothelial cell permeability. Mol Cell 39(3):468–476PubMedCrossRef

21.

Xue G, Zhang J, Zhang H, Zhang B, Sun M (2004) eNOS gene transfected endothelial cells inhibit smooth muscle cell proliferation and platelet aggregation in vitro. Mol Ther 9(5):150–S150

22.

Kader KN, Akella R, Ziats NP, Lakey LA, Harasaki H, Ranieri JP et al (2000) eNOS-overexpressing endothelial cells inhibit platelet aggregation and smooth muscle cell proliferation in vitro. Tissue Eng 6(3):241–251PubMedCrossRef

23.

Vanhoutte PM (1997) Endothelial dysfunction and atherosclerosis. Eur Heart J 18(Suppl. E):E19–E29PubMedCrossRef

24.

Duplain H, Burcelin R, Sartori C, Cook S, Egli M, Lepori M, Vollenweider P, Pedrazzini T, Nicod P, Thorens B, Scherrer U (2001) Insulin resistance, hyperlipidemia, and hypertension in mice lacking endothelial nitric oxide synthase. Circulation 104:342–345PubMedCrossRef

25.

Kumar RG, Spurthi MK, Kumar KG (2012) Endothelial nitric oxide synthase polymorphism G298T in association with oxidative DNA damage in coronary atherosclerosis. J Genet 91(3):349–352PubMedCrossRef

26.

Lembo G, Luca ND, Battagli C, Iovino G, Aretini A, Musicco M et al (2001) A common variant of endothelial nitric oxide synthase (Glu298Asp) is an independent risk factor for carotid atherosclerosis. Stroke 32(3):735–740PubMedCrossRef

27.

Zhang J, Guan X, Liang R (2011) Study of association between G894T polymorphism of endothelial nitric oxide synthase gene and carotid atherosclerisis. Chin J Geriatr Heart Brain Vessel Dis 13(7):633–636

28.

Asakimori Y, Yorioka N, Tanaka J, Kohno N (2003) Effect of polymorphism of the endothelial nitric oxide synthase and apolipoprotein E genes on carotid atherosclerosis in hemodialysis patients. Am J Kidney Dis 41(4):822–832PubMedCrossRef

29.

Wolff B, Braun C, Schlüter C, Grabe HJ, Popowski K, Völzke H et al (2005) Endothelial nitric oxide synthase Glu(298)→Asp polymorphism, carotid atherosclerosis and intima-media thickness in a general population sample. Clin Sci 109(5):475–481CrossRef

30.

Djuri T, UmiEvi M, KonAr I, Zivkovi M, Vasi D, Davidovi L et al (2009) Lack of association between eNOS Glu298Asp gene polymorphism and carotid atherosclerosis in a Serbian population. Clin Chem Lab Med 47(12):1573–1575

31.

Fatini C, Sofi F, Gensini F, Sticchi E, Lari B, Pratesi G et al (2004) Influence of eNOS gene polymorphisms on carotid atherosclerosis. Eur J Vasc Endovasc Surg 27(5):540–544PubMedCrossRef

32.

Zhang J, Guan X, Liang R (2012) Association of 4b/a and T786C polymorphism of endothelial nitric oxide synthase gene and carotid atherosclerosis. J Clin Cardiol 28(7):541–545

33.

Yijiang H, Zhao X, Shikun G, Xiangbo Y, Zhongrong L, Shian-Ying S (2017) Laparoscopically assisted anorectal pull-through versus posterior sagittal anorectoplasty for high and intermediate anorectal malformations: a systematic review and meta-analysis. PLoS ONE 12:e170421CrossRef

34.

Lu RC, Hao W, Yu JT (2011) Association study between the polymorphisms of nitric oxide synthase gene and carotid atherosclerosis in type 2 diabetic in the chinese han population. Chin J Nerv Mental Dis 37(11):683–686

35.

Messner B, Bernhard D (2014) Smoking and cardiovascular disease: mechanisms of endothelial dysfunction and early atherogenesis. Arterioscler Thromb Vasc Biol 34(3):509–515PubMedCrossRef

36.

Rubbo H, O’Donnell V (2005) Nitric oxide, peroxynitrite and lipoxygenase in atherogenesis: mechanistic insights. Toxicology 208(2):305–317PubMedCrossRef

37.

Cooke JP, Tsao P (1992) Cellular mechanisms of atherogenesis and the effects of nitric oxide. Curr Opin Cardiol 7(5):799–804CrossRef

38.

Cabrera M, López GV, Gómez LE, Breijo M, Pintos C et al (2011) Genetic toxicology and preliminary in vivo studies of nitric oxide donor tocopherol analogs as potential new class of antiatherogenic agents. Drug Chem Toxicol 34(3):285–293PubMedCrossRef

39.

Nishio E, Watanabe Y (1996) Glucose-induced down-regulation of NO production and inducible NOS expression in cultured rat aortic vascular smooth muscle cells: role of protein kinase C. Biochem Biophys Res Commun 229(3):857–863PubMedCrossRef

40.

Gellman MD, Turner JR (2013) Endothelial Nitric Oxide Synthase (eNOS). Arterioscler Thromb Vasc Biol 26(2):267–271

41.

Gellman MD (2008) Neuronal nitric oxide synthase (nNOS). Sci Bus eXchange 1(40):1326–1326

42.

Lechner M, Lirk P, Rieder J (2005) Inducible nitric oxide synthase (inos) in tumor biology: the two sides of the same coin. Semin Cancer Biol 15(4):277–289PubMedCrossRef

43.

Gornik HL, Creager MA (2004) Arginine and endothelial and vascular health. J Nutr 134(10):2880S–2887SPubMedCrossRef

44.

Karvonen J, Kauma H, Kervinen K, Rantala M, Kesäniemi YA (2010) Endothelial nitric oxide synthase gene Glu298Asp polymorphism and blood pressure, left ventricular mass and carotid artery atherosclerosis in a population-based cohort. J Intern Med 251(2):102–110CrossRef

45.

Rossi GP, Taddei S, Virdis A, Cavallin M, Ghiadoni L, Favilla S et al (2003) The T‑786C and Glu298Asp polymorphisms of the endothelial nitric oxide gene affect the forearm blood flow responses of Caucasian hypertensive patients. J Am Coll Cardiol 41(6):938–945PubMedCrossRef

46.

Wang XL, Sim AS, Badenhop RF, Mccredie RM, Wilcken DEL (1996) A smoking dependent risk of coronary artery disease associated with a polymorphism of the endothelial nitric oxide synthase gene. Nat Med 2(1):41–45PubMedCrossRef

47.

Nakayama M, Yasue H, Yoshimura M, Shimasaki Y, Kugiyama K, Ogawa H et al (1999) T786C mutation in the 5′-flanking region of the endothelial nitric oxide synthase gene is associated with coronary spasm. Circulation 99(22):2864–2870PubMedCrossRef

48.

Bernini M, Biondi ML, Demonti M, Ghilardi G, Guagnellini E, Massaro F et al (2002) Independent risk factor for moderate to severe internal carotid artery stenosis: T786C mutation of the endothelial nitric oxide synthase gene. Clin Chem 48(7):989–993PubMedCrossRef

49.

Spoto B, Benedetto FA, Testa A, Tripepi G, Mallamaci F, Maas R et al (2007) An additive effect of endothelial nitric oxide synthase gene polymorphisms contributes to the severity of atherosclerosis in patients on dialysis. Am J Hypertens 20(7):758–763PubMedCrossRef

50.

Wang XL, Mahaney MC, Sim AS, Wang J, Wang J, Blangero J et al (1997) Genetic contribution of the endothelial constitutive nitric oxide synthase gene to plasma nitric oxide levels. Arterioscler Thromb Vasc Biol 17(11):3147–3153PubMedCrossRef

51.

Tsukada T, Yokoyama K, Arai T, Takemoto F, Hara S, Yamada A et al (1998) Evidence of association of the ecNOS gene polymorphism with plasma NO metabolite levels in humans. Biochem Biophys Res Commun 245(1):190–193PubMedCrossRef

52.

Paternoster L, Martinez-Gonzalez NA, Charleton R, Chung M, Lewis S, Sudlow CLM (2010) Genetic effects on carotid intima-media thickness: systematic assessment and meta-analyses of candidate gene polymorphisms studied in more than 5000 subjects. Circ Cardiovasc Genet 3(1):15–21PubMedCrossRef

53.

Sen F, Demirturk M, Abaci N, Golcuk E, Oflaz H, Elitok A et al (2008) Endothelial nitric oxide synthase intron 4a/b polymorphism and early atherosclerotic changes in hypopituitary GH-deficient adult patients. Eur J Endocrinol 158(5):615–622PubMedCrossRef

54.

Schmidt W, Heinicke K, Wolfarth B, Heinicke I (2003) Endothelial nitric oxide synthase (ecNOS) 4a/b gene polymorphism and carotid artery intima-media thickness in type‑1 diabetic patients. Exp Clin Endocrinol Diabetes 111(1):12–15CrossRef

55.

Yoshimura M, Yasue H, Nakayama M (2000) Genetic risk factors for coronary artery spasm: significance of endothelial nitric oxide synthase gene T786C and missense Glu298Asp variants. J Investig Med 48(5):367–374PubMed

56.

Yoon S, Shin C, Park HY, Moon J, Kim E, Kim HT et al (2005) Endothelial nitric oxide synthase gene is associated with vessel stenosis in Korean population. Clin Chim Acta 353(1):177–185PubMedCrossRef

57.

Zhao Q, Su S, Chen S, Li B, Gu D (2006) Association study of the endothelial nitric oxide synthase gene polymorphisms with essential hypertension in northern Han Chinese. Chung Hua I Hsueh Tsa Chih 119(13):1065–1071

58.

Nakayama M, Yasue H, Yoshimura M, Shimasaki Y, Ogawa H, Kugiyama K et al (2000) 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 86(6):628–634PubMedCrossRef

59.

Wang J, Dudley D, Wang XL (2002) Haplotype-specific effects on endothelial NO synthase promoter efficiency: modifiable by cigarette smoking. Arterioscler Thromb Vasc Biol 22(5):e1–e4PubMedPubMedCentral

Titel: Genetic association between eNOS gene polymorphisms and risk of carotid atherosclerosis
A meta-analysis
verfasst von: Yongheng Chen
Lin Chen
Qiliang Zhou
Publikationsdatum: 23.10.2020
Verlag: Springer Medizin
Erschienen in: Herz / Ausgabe Sonderheft 2/2021
Print ISSN: 0340-9937
Elektronische ISSN: 1615-6692
DOI: https://doi.org/10.1007/s00059-020-04995-z

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