Distribution of the Leu33Pro polymorphisms of the ITGB3 gene and the Thr715Pro polymorphisms of the SELP gene in the population of healthy individuals and patients with coronary artery disease

Ischemic heart disease (IHD) remains a leading cause of mortality and disability worldwide despite advances in treatment. Genetic factors (polymorphisms of the genes) play a significant role in the pathogenesis of IHD. Studying polymorphisms may improve understanding of genetic predisposition to IHD and aid in personalizing therapeutic approaches.

The aim of the study is to investigate the distribution of genotypes and alleles of the Leu33Pro (rs5918) polymorphism in the ITGB3 gene and the Thr715Pro (rs6136) polymorphism in the SELP gene in groups of patients with IHD and healthy individuals.

The study included 209 participants divided into three groups: healthy individuals (n = 31), patients with chronic IHD without indications for invasive coronary angiography (n = 30), and patients with IHD who underwent elective PCI (n = 148). Genotyping of ITGB3 (Leu33Pro) and SELP (Thr715Pro) polymorphisms was performed using polymerase chain reaction with reagent kits manufactured by “Syntol” (Russia). Statistical analysis was conducted using the StatSoft STATISTICA 10.0 software. Non-parametric methods, including the Mann–Whitney test, Kruskal–Wallis test, and Fisher’s exact test, were used; the level of statistical significance was set at p < 0.05.

The study demonstrated that the distribution of genotypes and alleles of the Leu33Pro (rs5918) polymorphism in the ITGB3 gene and the Thr715Pro (rs6136) polymorphism in the SELP gene in the studied population, as well as in each group, conforms to Hardy–Weinberg equilibrium. Analysis of genotype and allele frequencies across codominant, dominant, recessive, and overdominant inheritance models revealed no statistically significant differences between the groups. For the Leu33Pro (T˃C, rs5918) polymorphism in the ITGB3 gene, allele T predominated (ranging from 79.53 to 82.76 %); however, intergroup differences in genotypes and alleles did not reach statistical significance. A similar pattern was observed for the Thr715Pro (rs6136) polymorphism in the SELP gene, where genotype and allele frequencies did not differ between groups in any of the inheritance models analyzed.

The results of this study revealed no statistically significant differences in the distribution of genotypes and alleles for the two investigated polymorphisms (Leu33Pro (rs5918) in the ITGB3 gene and Thr715Pro (rs6136) in the SELP gene) between patients and healthy individuals. The absence of statistically significant differences highlights the importance of further largescale studies considering ethnic, and other risk factors.

1. Andreassi M. G., Adlerstein D., Carpeggiani C., Shehi E., Fantinato S., Ghezzi E., Botto N., Coceani M., L’abbate A. Individual and summed effects of high-risk genetic polymorphisms on recurrent cardiovascular events following ischemic heart disease. Atherosclerosis, 2012, vol. 223, no. 2, pp. 409–415. https://doi.org/10.1016/j.atherosclerosis.2012.05.029

2. Reiner A. P., Carlson C. S., Thyagarajan B., Rieder M. J., Polak J. F., Siscovick D. S., Nickerson D. A, Jacobs D. R. Jr, Gross M. D. Soluble P-selectin, SELP polymorphisms, and atherosclerotic risk in European-American and African-African young adults: the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Arteriosclerosis, Thrombosis, and Vascular Biology, 2008, vol. 28, no. 8, pp. 1549–1555. https://doi.org/10.1161/ATVBAHA.108.169532

3. Kekomäki S., Hämäläinen L., Kauppinen-Mäkelin R., Palomäki H., Kaste M., Kontula K. Genetic polymorphism of platelet glycoprotein IIIa in patients with acute myocardial infarction and acute ischaemic stroke. Journal of Cardiovascular Risk, 1999, vol. 6, no. 1, pp. 13–17. https://doi.org/10.1177/204748739900600103

4. Herrera-Maya G., Vargas-Alarcón G., Pérez-Méndez O., Posadas-Sánchez R., Masso F., Juárez-Cedillo T., Escobedo G., Vázquez-Montero A., Fragoso J. M. The Ser290Asn and Thr715Pro polymorphisms of the selp gene are associated with a lower risk of developing acute coronary syndrome and low soluble P-selectin levels in a mexican population. Biomolecules, 2020, vol. 10, no. 2, p. 270. https://doi.org/10.3390/biom10020270

5. Volcik K. A., Ballantyne C. M., Coresh J., Folsom A. R., Wu K. K., Boerwinkle E. P-selectin Thr715Pro polymorphism predicts P-selectin levels but not risk of incident coronary heart disease or ischemic stroke in a cohort of 14595 participants: the Atherosclerosis Risk in Communities Study. Atherosclerosis, 2006, vol. 186, no. 1, pp. 74–79. https://doi.org/10.1016/j.atherosclerosis.2005.07.010

6. Payne K. E., Bray P. F., Grant P. J., Carter A. M. Beta3 integrin haplotype influences gene regulation and plasma von Willebrand factor activity. Atherosclerosis, 2008, vol. 198, no. 2, pp. 280–286. https://doi.org/10.1016/j.atherosclerosis.2007.10.005

7. Kucharska-Newton A. M., Monda K. L., Campbell S., Bradshaw P. T., Wagenknecht L. E., Boerwinkle E., Wasserman B. A., Heiss G. Association of the platelet GPIIb/IIIa polymorphism with atherosclerotic plaque morphology: the Atherosclerosis Risk in Communities (ARIC) Study. Atherosclerosis, 2011, vol. 216, no. 1, pp. 151–156. https://doi.org/10.1016/j.atherosclerosis.2011.01.038

8. Kou L, Yang N., Dong B., Li Y., Yang J., Qin Q. Interaction between SELP genetic polymorphisms with inflammatory cytokine interleukin-6 (IL-6) gene variants on cardiovascular disease in Chinese Han population. Mammalian Genome, 2017, vol. 28, no. 9–10, pp. 436–442. https://doi.org/10.1007/s00335-017-9712-9

9. Tuguz A., Tatarkova E., Rudenko K., Smolkov I., Shumilov D., Muzhenya D., Anokhina E., Ashkanova T. ITG and SEL genes polymorphisms associated with bronchial asthma, complications of peripheral and coronary atherosclerosis, and mammary adenocarcinoma among residents of the Republic of Adygea. Indian Journal of Science and Technology, 2015, vol. 8, no. 29, pp. 1–8. https://doi.org/10.17485/IJST/2015/V8I29/86841