ISSN 2412-4036 (print)
ISSN 2713-1823 (online)

Clinical and prognostic significance of NOS3 and APOE gene variants in patients with unstable angina pectoris

Dadova M.S., Kostenko V.A., Skorodumova E.A., Rysev A.V., Pivovarova L.P., Ariskina O.B., Siverina A.V., Skorodumova E.G., Koroleva M.I.

1) I.I. Dzhanelidze Saint Petersburg Research Institute of Emergency Care; 2) City Consultative and Diagnostic Center No. 1, Saint Petersburg
Abstract. The development of personalized medicine is associated with the study of genetic polymorphisms that determine the predisposition to cardiovascular diseases.
The aim: to assess the impact of APOE, NOS3 gene polymorphisms at the clinical course and prognosis (12 months) of patients with unstable angina pectoris (UAP).
Material and methods. Case histories and examination data of 100 patients with UAP treated at I.I. Dzhanelidze Saint Petersburg research institute of emergency care from 2022 to 2024 were studied. The remote results after 12 months were assessed: frequency of rehospitalizations for acute coronary syndrome (ACS), paroxysmal atrial fibrillation (AF), decompensations of chronic heart failure and acute cerebrovascular accident. Genetic testing of APOE, NOS3 was performed with division of the participants into 2 groups depending on the NOS3 gene polymorphism (T786C): Group 1 (n = 42) – CC/TC genotypes, Group 2 (n = 58) – TT genotype. The age and gender of patients were comparable in both groups.
Results. The frequency of occurrence of NOS3 gene variants in the general group was as follows: CC – in 4%, TC – in 38%, TT – in 58% of patients. Distribution by the APOE gene: LeuLeu in 75% of participants, the rest – heterozygous LeuPro. TC/CC NOS3 carriers were more likely to have had myocardial infarction and percutaneous coronary intervention in the past, more severe coronary artery disease, worsening of chronic renal disease and high levels of C-reactive protein, indicating a pronounced systemic inflammatory response. LeuPro APOE carriers were found to have elevated levels of total cholesterol, low-density lipoproteins in the blood and a higher frequency of multifocal atherosclerosis. Patients with the TC/CC NOS3 genotype had an increased risk of recurrent ACS and paroxysmal AF within a year.
Conclusion. Genotypes CC and TC NOS3 are associated with severe clinical course of the disease and evident systemic inflammation. Genotype TC/CC NOS3 increases the risk of recurrent ACS and AF within a year. Polygenic carriage of recessive alleles of the NOS3 and APOE genes worsens the prognosis of patients in short- and long-term perspective.

Keywords

unstable angina pectoris
long-term prognosis
gene polymorphism
NOS3
APOE

References

1. Li J, Wu X, Li X, Feng G, He L, Shi Y. The endothelial nitric oxide synthase gene is associated with coronary artery disease: A meta-analysis. Cardiology. 2010;116(4):271–78.

PMID: 20861627. https://doi.org/10.1159/000316063

2. Бебякова Н.А., Первухина О.А., Фадеева Н.А., Хромова А.В. Полиморфизм генов AGT, AGT2R1 и NOS3 как фактор риска развития дисбаланса вазоактивных факторов. Экология человека. 2020;(10):4–9. (Bebyakova NA, Pervukhina OA, Fadeeva NA, Khromova AV. Polymorphism of AGT, AGT2R1 and NOS3 genes as a risk factor for imbalance in vasoactive factors. Ekologiya cheloveka = Human Ecology. 2020;(10):4–9 (In Russ.)).

EDN: LWFSHN. https://doi.org/10.33396/1728-0869-2020-10-4-9

3. Груздева А.А., Хохлов А.Л., Ильин М.В., Поздняков Н.О., Мирошников А.Е. Полиморфизм генов NOS3 rs1799983, AGTR2 rs1403543 и стратификация риска сердечно-сосудистых осложнений у больных ишемической болезнью сердца. Вятский медицинский вестник. 2021;(1):4–10. (Gruzdeva AA, Khokhlov AL, Ilyin MV, Pozdnyakov NO, Miroshnikov AE. Polymorphism of NOS3 rs1799983, AGTR2 rs1403543 genes and risk stratification of cardiovascular complications in patients with coronary heart disease. Vyatskiy meditsinskiy vestnik = Medical Newsletter of Vyatka. 2021;(1):4–10 (In Russ.)).

EDN: IVGWZA. https://doi.org/10.24411/2220-7880-2021-10142

4. Дунай В.И., Глинская Н.А., Жук О.Н., Сильченко Е.С. Полиморфизм гена NOS3 эндотелиальной (еNOS) синтазы оксида азота как предиктор формирования сосудистых патологий. Вестник Полесского государственного университета. Серия природоведческих наук. 2024;(1):56–65. (Dunai VI, Glinskaya NA, Zhuk ON, Silchenko ES. Polymorphism of the NOS3 gene of endothelial (eNOS) nitric oxide synthase as a predictor of the formation of vascular pathologies. Vestnik Polesskogo gosudarstvennogo universiteta. Seriya prirodovedcheskih nauk = Bulletin of Polessky State University. Series in Natural Sciences. 2024;(1):56–65 (In Russ.)). EDN: ANBWMA.

5. Афиногенова О.А. Полиморфизм -786T>C гена NOS3 в развитии вазоконстрикции (обзор). Фундаментальные и прикладные научные исследования: актуальные вопросы, достижения и инновации. Сборник статей XXXVI Международной научно-практической конференции: в 2 ч. Часть 1. Пенза: Наука и просвещение (ИП Гуляев Г.Ю.). 2020:38–44. (Afinogenova OA. Polymorphism -786T>C of the NOS3 gene in the development of vasoconstriction (review). Fundamental and applied scientific research: Current issues, achievements and innovations. Collection of articles of the XXXVI International Scientific and Practical Conference: At 2 parts. Part 1. Penza: Science and Enlightenment (IP Gulyaev G.Yu.). 2020:38–44 (In Russ.)). EDN: PMTHQX.

6. Casas JP, Cavalleri GL, Bautista LE, Smeeth L, Humphries SE, Hingorani AD. Endothelial nitric oxide synthase gene polymorphisms and cardiovascular disease: A HuGE review. Am J Epidemiol. 2006;164(10):921–35.

PMID: 17018701. https://doi.org/10.1093/aje/kwj302

7. Rossi GP, Taddei S, Virdis A, Cavallin M, Ghiadoni L, Favilla S et al. 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. 2003;41(6):938–45.

PMID: 12651037. https://doi.org/10.1016/s0735-1097(02)03011-5

8. Ragia G, Nikolaidis E, Tavridou A, Arvanitidis KI, Kanoni S, Dedoussis GV et al. Endothelial nitric oxide synthase gene polymorphisms -786T>C and 894G>T in coronary artery bypass graft surgery patients. Hum Genomics. 2010;4(6):375–83.

PMID: 20846926. PMCID: PMC3525225. https://doi.org/10.1186/1479-7364-4-6-375

9. The ALlele FREquency Database. URL: http://alfred.med.yale.edu (date of access – 19.08.2025).

10. Casas JP, Bautista LE, Humphries SE, Hingorani AD. Endothelial nitric oxide synthase genotype and ischemic heart disease: Meta-analysis of 26 studies involving 23028 subjects. Circulation. 2004;109(11):1359–65.

PMID: 15007011. https://doi.org/10.1161/01.cir.0000121357.76910.A3

11. Tanus-Santos JE, Desai M, Flockhart DA. Effects of ethnicity on the distribution of clinically relevant endothelial nitric oxide variants. Pharmacogenetics. 2001;11(8):719–25.

PMID: 11692081. https://doi.org/10.1097/00008571-200111000-00011

12. Miyaki K, Tohyama S, Murata M, Kikuchi H, Takei I, Watanabe K, Omae K. Salt intake affects the relation between hypertension and the T-786C polymorphism in the endothelial nitric oxide synthase gene. Am J Hypertens. 2005;18(12 Pt 1):1556–62.

PMID: 16364825. https://doi.org/10.1016/j.amjhyper.2005.06.012

13. Кононов С.И., Маль Г.С., Чурилин М.И., Азарова Ю.Э., Клесова Е.Ю., Быканова М.А., Полоников А.В. Полиморфный вариант rs7412 гена APOE как маркер риска развития ишемической болезни сердца и эффективности терапии розувастатином. Человек и его здоровье. 2019;(1):5–13. (Kononov SI, Mal GS, Churilin MI, Azarova YuE, Klesova EYu, Bykanova MA, Polonikov AV. Polymorphic rs7412 in APOE gene as a predictor of ischemic heart disease risk and effectiveness of rosuvastatin therapy. Chelovek i ego zdorov’e = Humans and Their Health». 2019;(1):5–13 (In Russ.)).

EDN: ZXWFRJ. https://doi.org/10.21626/vestnik/2019-1/01

14. Сиверина А.В., Скородумова Е.А., Костенко В.А., Пивоварова Л.П., Малышев М.Е., Арискина О.Б. с соавт. Влияние полиморфизма генов APOE и SLCO1B1 на течение инфаркта миокарда, ассоциированного с острым повреждением почек, в стационаре и отдаленном периоде. Нефрология. 2018;22(6):56–63. (Siverina AV, Skorodumova EA, Kostenko VA, Pivovarova LP, Malyshev ME, Ariskina OB et al. Effect of polymorphism of APOE and SLCO1B1 genes on the course of myocardial infarction associated with acute kidney injury in hospital and long-term periods. Nefrologiya = Nephrology (Saint Petersburg). 2018;22(6):56–63 (In Russ.)).

EDN: YUBOVF. https://doi.org/10.24884/1561-6274-2018-22-6-56-63

15. Дадова М.С., Костенко В.А., Скородумова Е.А., Рысев А.В., Бакаев И.A., Сиверина А.В., Скородумова Е.Г. Современный портрет пациента с нестабильной стенокардией: новые тренды. Скорая медицинская помощь. 2024;25(3):85–91. (Dadova MS, Kostenko VA, Skorodumova EA, Rysev AV, Bakaev IA, Siverina AV, Skorodumova EG. Modern portrait of a patient with unstable angina pectoris: New trends. Skoraya meditsinskaya pomoshch = Emergency Medical Care. 2024;25(3):85–91 (In Russ.)).

EDN: PTRVBC. https://doi.org/10.24884/2072-6716-2024-25-3-85-91

16. Муслимова Э.Ф., Реброва Т.Ю., Афанасьев С.А., Сергиенко Т.Н., Репин А.Н. Генотип -786CC гена эндотелиальной NO-синтазы NOS3 как фактор неблагоприятного течения ишемической болезни сердца и риска повышенной агрегации тромбоцитов на фоне приема антиагрегантов. Российский кардиологический журнал. 2017;22(10):29–32. (Muslimova EF, Rebrova TYu, Afanasyev SA, Sergienko TN, Repin AN. Genotype -786CC of the NOS3 endothelial NO synthase gene as a factor in the unfavorable course of coronary heart disease and the risk of increased platelet aggregation while taking antiplatelet agents. Rossiyskiy kardiologicheskiy zhurnal = Russian Journal of Cardiology. 2017;22(10):29–32 (In Russ.)).

EDN: ZULXBJ. https://doi.org/10.15829/1560-4071-2017-10-29-32

About the Authors

Marianna S. Dadova, MD, postgraduate seeker for the degree of PhD (Medicine) at I.I. Dzhanelidze Saint Petersburg Research Institute of Emergency Care, cardiologist at Saint Petersburg City Consultative and Diagnostic Center No. 1. Address: 192242, Saint Petersburg, 3, litera A Budapestskaya St.
E-mail: dadova78@gmail.com
ORCID: https://orcid.org/0009-0009-3922-1971. eLibrary SPIN: 8709-6885
Victor A. Kostenko, MD, Dr. Sci. (Medicine), head of the Department of emergency cardiology and rheumatology, I.I. Dzhanelidze Saint Petersburg Research Institute of Emergency Care. Address: 192242, Saint Petersburg, 3, litera A Budapestskaya St.
E-mail: vic2012tor@mail.ru
ORCID: https://orcid.org/0000-0002-7015-1010. eLibrary SPIN: 2774-0835
Elena A. Skorodumova, MD, Dr. Sci. (Medicine), leading researcher at the Department of emergency cardiology and rheumatology, I.I. Dzhanelidze Saint Petersburg Research Institute of Emergency Care. Address: 192242, Saint Petersburg, 3, litera A Budapestskaya St.
E-mail: elskor@mail.ru
ORCID: https://orcid.org/0000-0002-5017-0214. eLibrary SPIN: 6393-1178
Alexander V. Rysev, MD, PhD (Medicine), associate professor, deputy chief physician for therapy, I.I. Dzhanelidze Saint Petersburg Research Institute of Emergency Care. Address: 192242, Saint Petersburg, 3, litera A Budapestskaya St.
E-mail: 79213221618@yandex.ru
ORCID: https://orcid.org/0000-0001-8261-2438. eLibrary SPIN: 7715-0455
Lyudmila P. Pivovarova, MD, Dr. Sci. (Medicine), head of the Department of laboratory diagnostics, I.I. Dzhanelidze Saint Petersburg Research Institute of Emergency Care. Address: 192242, Saint Petersburg, 3, litera A Budapestskaya St.
E-mail: pivovaroval@yandex.ru
ORCID: https://orcid.org/0000-0002-9492-4516. eLibrary SPIN: 2832-3106
Olga B. Ariskina, PhD (Biology), researcher at the Department of laboratory diagnostics, I.I. Dzhanelidze Saint Petersburg Research Institute of Emergency Care. Address: 192242, Saint Petersburg, 3, litera A Budapestskaya St.
E-mail: olga.ariskina@mail.ru
ORCID: https://orcid.org/0000-0001-6311-1259. eLibrary SPIN: 6067-8268
Anna V. Siverina, MD, PhD (Medicine), researcher at the Department of emergency cardiology and rheumatology, I.I. Dzhanelidze Saint Petersburg Research Institute of Emergency Care. Address: 192242, Saint Petersburg, 3, litera A Budapestskaya St.
E-mail: gudkovanna_09@mail.ru
ORCID: https://orcid.org/0000-0002-6831-2153. eLibrary SPIN: 7817-1246
Elizaveta G. Skorodumova, MD, PhD Medicine), junior researcher at the Department of emergency cardiology and rheumatology, I.I. Dzhanelidze Saint Petersburg Research Institute of Emergency Care. Address: 192242, Saint Petersburg, 3, litera A Budapestskaya St.
E-mail: lisavetta91@mail.ru
ORCID: https://orcid.org/0000-00024961-5570. eLibrary SPIN: 3403-2138
Maria I. Koroleva, MD, head of the Department of cardiology, cardiologist at Saint Petersburg City Consultative and Diagnostic Center No. 1. Address: 194354, Saint Petersburg, 10 Seikerosa St.
E-mail: bizeshka92@mail.ru
ORCID: https://orcid.org/0009-0003-4687-1661

Similar Articles

By continuing to use our site, you consent to the processing of cookies that ensure the proper functioning of the site.