Some molecular genetic markers of progressive atherosclerosis in patients with coronary heart disease

The aim of the study is to evaluate the association of some molecular genetic markers with progressive atherosclerosis. 
Material and methods. In total, the study included 202 patients (147 men and 55 women), who were divided into 2 groups. The 1st (main) group included patients with coronary artery disease (100 people) who had a combination of two or more cardiovascular events during the last 2 years before inclusion: myocardial infarction or unstable angina pectoris, arterial stenting for urgent indications (coronary and peripheral), stroke; acute ischemia, thrombosis or amputation of the lower extremities. The 2nd group (comparisons) included 102 patients with coronary artery disease who did not have any of the above cardiovascular events during the last 2 years before inclusion. DNA was isolated from peripheral blood samples by phenol-chloroform extraction. 
Results. According to the frequencies of genotypes of the I/D polymorphism (rs36232792) of the SOD1 gene, no statistically significant differences were obtained between the group with progressive atherosclerosis and the control, neither in general, nor when divided by sex and age. The odds ratio of developing progressive atherosclerosis in carriers of the rare homozygous DD genotype of the rs3834129 polymorphism of the CASP8 gene is 2.3 ne is 2.3 times higher compared to carriers of the other two genotypes (DD vs II + ID, 95 % CI 1.1–5.1; p = 0.037). In men, the odds ratio is higher than in the general group – 4.4, p = 0.015. Women also tend to accumulate carriers of the DD genotype in the group with progressive atherosclerosis (26.7 % vs 16.0 %), but the differences do not reach the level of statistical significance. 
Conclusions. The carriage of the DD genotype of the rs3834129 polymorphism of the CASP8 gene is associated with progressive atherosclerosis in patients with CAD. No association of I/D polymorphism (rs36232792) of the SOD1 gene with progressive atherosclerosis was found. Acknowledgments. The molecular genetic fragment of the study was supported by State Budget theme no. 122031700094-5.

1. Piepoli M.F., Hoes A.W., Agewall S., Albus C., Brotons C., Catapano A.L., Cooney M.T., Corrà U., Cosyns B., Deaton C., Graham I., Hall M.S., Hobbs F.D.R., Løchen M.L., Löllgen H., MarquesVidal P., Perk J., Prescott E., Redon J., Richter D.J., Sattar N., Smulders Y., Tiberi M., van der Worp H.B., van Dis I., Verschuren W.M.M. 2016 European guidelines on cardiovascular disease prevention in clinical practice. The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts. Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). G. Ital. Cardiol. (Rome), 2017; 18 (7): 547–612. (In Ital.). Linee guida europee 2016 sulla prevenzione delle malattie cardiovascolari nella pratica clinica. Sesta Task Force congiunta della Società Europea di Cardiologia e di altre Società sulla Prevenzione delle Malattie Cardiovascolari nella Pratica Clinica (costituita da rappresentanti di 10 società e da esperti invitati). Redatte con il contributo straordinario dell’Associazione Europea per la Prevenzione e Riabilitazione Cardiovascolare (EACPR). doi: 10.1714/2729.27821

2. Hasturk H., Abdallah R., Kantarci A., Nguyen D., Giordano N., Hamilton J., van Dyke T.E. Resolvin E1 (RvE1) attenuates atherosclerotic plaque formation in diet and inflammation-induced atherogenesis. Arterioscler. Thromb. Vasc. Biol., 2015; 35 (5): 1123–1133. doi: 10.1161/ATVBAHA.115.305324

3. Herrington W., Lacey B., Sherliker P., Armitage J., Lewington S. Epidemiology of atherosclerosis and the potential to reduce the global burden of atherothrombotic disease. Circ. Res., 2016; 118 (4): 535–546. doi: 10.1161/CIRCRESAHA.115.307611

4. Darroudi S., Tajbakhsh A., Esmaily H., Ghazizadeh H., Zamani P., Sadabadi F., Tayefi M., Tayefi B., Fereydouni N., Mouhebati M., Akbari Sark N., Avan A., Ferns G.A., Mohammadpour A.H., Asadi Z., Ghayour-Mobarhan M. 50 bp deletion in promoter superoxide dismutase 1 gene and increasing risk of cardiovascular disease in Mashhad stroke and heart atherosclerotic disorder cohort study. Biofactors, 2020; 46 (1): 55–63. doi: 10.1002/biof.1575

5. Milani P., Gagliardi S., Bongioanni P., Grieco G.S., Dezza M., Bianchi M., Cova E., Ceroni M., Cereda C. Effect of the 50 bp deletion polymorphism in the SOD1 promoter on SOD1 mRNA levels in Italian ALS patients. J. Neurol. Sci., 2012; 313 (1-2): 75–78. doi: 10.1016/j.jns.2011.09.026

6. Neves A.L., Mohammedi K., Emery N., Roussel R., Fumeron F., Marre M., Velho G. Allelic variations in superoxide dismutase-1 (SOD1) gene and renal and cardiovascular morbidity and mortality in type 2 diabetic subjects. Mol. Genet. Metab., 2012; 106 (3): 359–635. doi: 10.1016/j.ymgme.2012.04.023

7. Otaki Y., Watanabe T., Nishiyama S., Takahashi H., Arimoto T., Shishido T., Miyamoto T., Konta T., Shibata Y., Sato H., Kawasaki R., Daimon M., Ueno Y., Kato T., Kayama T., Kubota I. The impact of superoxide dismutase-1 genetic variation on cardiovascular and all-cause mortality in a prospective cohort study: The Yamagata (Takahata) study. PLoS One, 2016; 11 (10): e0164732. doi: 10.1371/journal.pone.0164732

8. Eskandari-Nasab E., Kharazi-Nejad E., Nakhaee A., Afzali M., Tabatabaei S.P., Tirgar-Fakheri K., Hashemi M. 50-bp Ins/Del polymorphism of SOD1 is associated with increased risk of cardiovascular disease. Acta Med. Iran, 2014; 52 (8): 591–595.

9. Privé F., Aschard H., Carmi S., Folkersen L., Hoggart C., O’Reilly P.F., Vilhjálmsson B.J. Portability of 245 polygenic scores when derived from the UK Biobank and applied to 9 ancestry groups from the same cohort. Am. J. Hum. Genet., 2022; 109 (1): 12–23. doi: 10.1016/j.ajhg.2021.11.008

10. http://phgkb.cdc.gov/PHGKB/startPagePedia.action

11. http://omim.org/

12. Erdman V.V., Nasibullin T.R., Tuktarova I.A., Mustafina O.E. Association of polymorphic markers of CASP8, BCL2 and BAX genes with aging and longevity. Adv. Gerontol., 2012; 25 (3): 398–404. (In Russ.).

13. Gundapaneni K.K., Shyamala N., Galimudi R.K., Kupsal K., Gantala S.R., Padala C., Gunda P., Tupurani M.A., Puranam K., Sahu S.K., Hanumanth S.R. Polymorphic variants of Caspase genes (8 & 3) in the risk prediction of Coronary Artery Disease. Gene, 2017; 627: 278–283. doi: 10.1016/j.gene.2017.06.035

14. Helseth R., Weiss T.W., Opstad T.B., Siegbahn A., Solheim S., Freynhofer M.K., Huber K., Arnesen H., Seljeflot S. Associations between circulating proteins and corresponding genes expressed in coronary thrombi in patients with acute myocardial infarction. Thromb. Res., 2015; 136 (6): 1240–1244. doi: 10.1016/j.thromres.2015.10.005

15. Liang Y., Lin Q., Zhu J., Li X., Fu Y., Zou X., Liu X., Tan H., Deng C., Yu X., Shan Z., Yuan W. The caspase-8 shRNA-modified mesenchymal stem cells improve the function of infarcted heart. Mol. Cell. Biochem., 2014; 397 (1-2): 7–16. doi: 10.1007/s11010-014-2165-5

16. Niu C., Chen Z., Kim K.T., Sun J., Xue M., Chen G., Li S., Shen Y., Zhu Z., Wang X., Liang J., Jiang C., Cong W., Jin L., Li X. Metformin alleviates hyperglycemia-induced endothelial impairment by downregulating autophagy via the Hedgehog pathway. Autophagy, 2019; 15 (5): 843–870. doi: 10.1080/15548627.2019.1569913

17. Cui S., Li W., Wang P., Lv X., Gao Y., Huang G. Folic acid inhibits homocysteine-induced cell apoptosis in human umbilical vein endothelial cells. Mol. Cell. Biochem., 2018; 444 (1-2): 77–86. doi: 10.1007/s11010-017-3232-5

18. Wehland M., Ma X., Braun M., Hauslage J., Hemmersbach R., Bauer J., Grosse J., Infanger M., Grimm D. The impact of altered gravity and vibration on endothelial cells during a parabolic flight. Cell Physiol. Biochem., 2013; 31 (2-3): 432–451. doi: 10.1159/000343380

19. Sun T., Gao Y., Tan W., Ma S., Shi Y., Yao J., Guo Y., Yang M., Zhang X., Zhang Q., Zeng C., Lin D. A six-nucleotide insertion-deletion polymorphism in the CASP8 promoter is associated with susceptibility to multiple cancers. Nat. Genet., 2007; 39 (5): 605–613. doi: 10.1038/ng2030

20. Pereira A., Mendonca M.I., Borges S., Sousa A.C., Freitas S., Henriques E., Rodrigues M., Freitas A.I., Guerra G., Freitas C., Pereira D., Brehm A., Reis R.P.D. Additional value of a combined genetic risk score to standard cardiovascular stratification. Genet. Mol. Biol., 2018; 41 (4): 766–774. doi: 10.1590/1678-4685-GMB-2017-0173