Coronary artery diseases comprise a spectrum of disorders affecting the heart and blood vessels, characterized by reduced blood supply to the heart, often resulting from narrowing or obstruction of the coronary arteries. These conditions arise from an interaction between environmental and genetic factors, including the endothelial nitric oxide synthase (eNOS) gene. This study aimed to investigate the involvement of eNOS gene polymorphism in the occurrence of coronary artery disease in the Beninese population of Cotonou. An unmatched case-control observational analytical study was conducted from June to December 2019. The G894T polymorphism (rs1799983) of the eNOS gene was analyzed using the restriction fragment length polymorphism (RFLP) technique, following DNA extraction from whole blood samples. Fasting hyperglycemia was observed in 28.9% of cases compared to 2.6% of controls, and Asp298/Asp298 homozygosity was found in 7.89% of cases versus 2.63% of controls. Although the difference was not statistically significant, a trend toward an association with cardiovascular pathology was observed. This study revealed a high frequency of metabolic abnormalities in cases compared to controls and suggests a potential association between Asp298 allele homozygosity of the eNOS gene and the occurrence of cardiovascular diseases. The G894T polymorphism (rs1799983) of the eNOS gene may play a role in reducing nitric oxide bioavailability and endothelial dysfunction.
References
[1]
World Health Organization (WHO) (2012) World Health Statistics 2025: Monitoring Health for the SDGs, Sustainable Development Goals.
[2]
N’Guetta, R., Yao, H., Ekou, A., N’Cho-Mottoh, M.P., Angoran, I., Tano, M., et al. (2016) Prévalence et caractéristiques des syndromes coronariens aigus dans une population d’Afrique subsaharienne. AnnalesdeCardiologieetd’Angéiologie, 65, 59-63. https://doi.org/10.1016/j.ancard.2016.01.001
[3]
Choukrallah, H., Choukrani, H., Mokri, A. and Benouna, G. (2022) La maladie coronarienne: Facteurs de risque et Traitement. InternationalJournalofMedicalReviewsandCaseReports, 6, 80-85. https://doi.org/10.5455/ijmrcr.lamaladiecoronarienne
[4]
Forstermann, U. and Sessa, W.C. (2011) Nitric Oxide Synthases: Regulation and Function. EuropeanHeartJournal, 33, 829-837. https://doi.org/10.1093/eurheartj/ehr304
[5]
Guerby, P. (2020) Dysfonction de la Nitric Oxide Synthase endothéliale au cours de la pré-éclampsie: Rôle du glutathion et du stress oxydant. Master’s Thesis, Université de Toulouse.
[6]
Shi, J., Liu, S., Guo, Y., Liu, S., Xu, J., Pan, L., et al. (2021) Association between Enos Rs1799983 Polymorphism and Hypertension: A Meta-Analysis Involving 14,185 Cases and 13,407 Controls. BMCCardiovascularDisorders, 21, Article No. 385. https://doi.org/10.1186/s12872-021-02192-2
[7]
Hingorani, A.D., Liang, C.F., Fatibene, J., Lyon, A., Monteith, S., Parsons, A., et al. (1999) A Common Variant of the Endothelial Nitric Oxide Synthase (Glu298→Asp) Is a Major Risk Factor for Coronary Artery Disease in the Uk. Circulation, 100, 1515-1520. https://doi.org/10.1161/01.cir.100.14.1515
[8]
Tesauro, M., Thompson, W.C., Rogliani, P., Qi, L., Chaudhary, P.P. and Moss, J. (2000) Intracellular Processing of Endothelial Nitric Oxide Synthase Isoforms Associated with Differences in Severity of Cardiopulmonary Diseases: Cleavage of Proteins with Aspartate vs. Glutamate at Position 298. Proceedings of the National Academy of Sciences of the United States of America, 97, 2832-2835. https://doi.org/10.1073/pnas.97.6.2832
[9]
Li, X., Lin, Y. and Zhang, R. (2018) Associations between Endothelial Nitric Oxide Synthase Gene Polymorphisms and the Risk of Coronary Artery Disease: A Systematic Review and Meta-Analysis of 132 Case-Control Studies. EuropeanJournalofPreventiveCardiology, 26, 160-170. https://doi.org/10.1177/2047487318780748
[10]
Shimasaki, Y., Yasue, H., Yoshimura, M., Nakayama, M., Kugiyama, K., Ogawa, H., et al. (1998) Association of the Missense Glu298asp Variant of the Endothelial Nitric Oxide Synthase Gene with Myocardial Infarction. JournaloftheAmericanCollegeofCardiology, 31, 1506-1510. https://doi.org/10.1016/s0735-1097(98)00167-3
[11]
Pacific BioSciences (2012) Extracting DNA Using Phenol-Chloroform Reagents Needed, 9-10.
Arafa, S., Abdelsalam, S., El-Gilany, A., Mosaad, Y.M. and Abdel-Ghaffar, A. (2018) Endothelial nitric oxide synthase Glu 298 Asp (G894T) and ApolipoproteinE Gene Polymorphism as Possible Risk Factors for Coronary Heart Disease among Egyptians. TheEgyptianHeartJournal, 70, 393-401. https://doi.org/10.1016/j.ehj.2018.08.001
[14]
Younan, H., Abdel Razek, G., Elkhashab, K., Abdelrasol, H. and Saad, M. (2015) Relationship of Endothelial Nitric Oxide Synthase Gene Polymorphism with Atherosclerotic Coronary and Carotid Arterial Disease in Egyptian Population. TheEgyptianHeartJournal, 67, 225-232. https://doi.org/10.1016/j.ehj.2014.01.003
[15]
Ahmmed, M.S., Shuvo, S.D., Paul, D.K., Karim, M.R., Kamruzzaman, M., Mahmud, N., et al. (2021) Prevalence of Dyslipidemia and Associated Risk Factors among Newly Diagnosed Type-2 Diabetes Mellitus (T2DM) Patients in Kushtia, Bangladesh. PLOSGlobalPublicHealth, 1, e0000003. https://doi.org/10.1371/journal.pgph.0000003
[16]
Sarnak, M.J. and Levey, A.S. (2000) Cardiovascular Disease and Chronic Renal Disease: A New Paradigm. AmericanJournalofKidneyDiseases, 35, S117-S131. https://doi.org/10.1016/s0272-6386(00)70239-3
[17]
Lv, S., Zhang, H., Chen, J., Shen, Z., Zhu, C., Gu, Y., et al. (2021) The Effect of Triglycerides to High-Density Lipoprotein Cholesterol Ratio on the Reduction of Renal Function: Findings from China Health and Retirement Longitudinal Study (CHARLS). LipidsinHealthandDisease, 20, Article No. 110. https://doi.org/10.1186/s12944-021-01542-5
[18]
Nagayama, D., Watanabe, Y., Yamaguchi, T., Fujishiro, K., Suzuki, K., Shirai, K., et al. (2023) Relationship of Serum Lipid Parameters with Kidney Function Decline Accompanied by Systemic Arterial Stiffness: A Retrospective Cohort Study. ClinicalKidneyJournal, 16, 2289-2298. https://doi.org/10.1093/ckj/sfad131
[19]
James, R.W. (2006) Rapports lipides/lipides et lipides/apolipoprotéines: Qu’apportent-ils au bilan cardiovasculaire? RevueMédicaleSuisse, 2, 632-632. https://doi.org/10.53738/revmed.2006.2.56.0632
[20]
Tsimihodimos, V., Mitrogianni, Z. and Elisaf, M. (2011) Dyslipidemia Associated with Chronic Kidney Disease. TheOpenCardiovascularMedicineJournal, 5, 41-48. https://doi.org/10.2174/1874192401105010041
[21]
Goligorsky, M.S. (2009) Endothelial Nitric Oxide Synthase: From Structure to Function in One Aspartic Substitution. KidneyInternational, 75, 255-257. https://doi.org/10.1038/ki.2008.605
[22]
Adjagba, M.O. (2019) Effets sur le réseau vasculaire artériel de trois plantes utilisées dans le traitement traditionnel de l’hypertension artérielle au Bénin. Master’s Thesis, Univesité d’Abomey-Calavi, Abomey-Calavi.
[23]
Napoli, C., de Nigris, F., Williams-Ignarro, S., Pignalosa, O., Sica, V. and Ignarro, L.J. (2006) Nitric Oxide and Atherosclerosis: An Update. NitricOxide, 15, 265-279. https://doi.org/10.1016/j.niox.2006.03.011
[24]
Vecoli, C., Caselli, C., Modena, M., Todiere, G., Poddighe, R., Valente, S., et al. (2024) Low HDL Cholesterol and the eNOS Glu298Asp Polymorphism Are Associated with Inducible Myocardial Ischemia in Patients with Suspected Stable Coronary Artery Disease. BMCCardiovascularDisorders, 24, Article No. 176. https://doi.org/10.1186/s12872-024-03846-7
[25]
Tian, G., Zeng, X., Wang, X., Zhang, L., Zhang, W. and Wei, W. (2013) Association between the Endothelial Nitric Oxide Synthase Gene Glu298Asp Polymorphism and Coronary Heart Disease: A Meta-Analysis of 39 Case-Control Studies. MolecularMedicineReports, 7, 1310-1318. https://doi.org/10.3892/mmr.2013.1301
[26]
Casas, J.P., Bautista, L.E., Humphries, S.E. and Hingorani, A.D. (2004) Endothelial Nitric Oxide Synthase Genotype and Ischemic Heart Disease: Meta-Analysis of 26 Studies Involving 23028 Subjects. Circulation, 109, 1359-1365. https://doi.org/10.1161/01.cir.0000121357.76910.a3
[27]
Bengel, F.M., Ueberfuhr, P., Schiepel, N., Nekolla, S.G., Reichart, B. and Schwaiger, M. (2001) Effect of Sympathetic Reinnervation on Cardiac Performance after Heart Transplantation. NewEnglandJournalofMedicine, 345, 731-738. https://doi.org/10.1056/nejmoa010519
[28]
Hibi, K., Ishigami, T., Tamura, K., Mizushima, S., Nyui, N., Fujita, T., et al. (1998) Endothelial Nitric Oxide Synthase Gene Polymorphism and Acute Myocardial Infarction. Hypertension, 32, 521-526. https://doi.org/10.1161/01.hyp.32.3.521
[29]
Luo, J., Wen, J., Zhou, H., Chen, X. and Zhang, W. (2014) Endothelial Nitric Oxide Synthase Gene G894T Polymorphism and Myocardial Infarction: A Meta-Analysis of 34 Studies Involving 21068 Subjects. PLOSONE, 9, e87196. https://doi.org/10.1371/journal.pone.0087196
[30]
Feingold, J. (2005) Maladies multifactorielles: Un cauchemar pour le généticien. Médecine/Sciences, 21, 927-933. https://doi.org/10.1051/medsci/20052111927
[31]
Fathelbab, H.T., Taie, A.S., Abd-Elatif, I., Ibrahim, S.M., Mowafy, A.H. and Faris, F.M. (2025) Impact of the Endothelial Nitric Oxide Synthase (eNOS) c.894 G > T Gene Polymorphism on Coronary Artery Dilatation Disease. TheEgyptianJournalofCriticalCareMedicine, 12, Article No. 12. https://doi.org/10.1007/s44349-025-00022-4
[32]
Taguchi, K. and Yamamoto, M. (2020) The KEAP1-NRF2 System as a Molecular Target of Cancer Treatment. Cancers, 13, Article 46. https://doi.org/10.3390/cancers13010046
[33]
Lembo, G., De Luca, N., 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, 735-740. https://doi.org/10.1161/01.str.32.3.735
[34]
Yoon, Y., Song, J., Hong, S.H.O. and Kim, J.Q. (2000) Plasma Nitric Oxide Concentrations and Nitric Oxide Synthase Gene Polymorphisms in Coronary Artery Disease. ClinicalChemistry, 46, 1626-1630. https://doi.org/10.1093/clinchem/46.10.1626