Genetic Polymorphism in Patients with Newly Diagnosed Type 2 Diabetes Mellitus

The aim of the research was to study the potential response to pharmacotherapy in patients with type 2 diabetes mellitus considering the single nucleotide polymorphisms in the genes encoding for endothelial nitric oxide synthase, 8-oxoguanine DNA glycosylase, and p53 protein as well as their combinations.

Materials and Methods. A total of 89 patients with newly diagnosed type 2 diabetes mellitus before the start of pharmacotherapy and 80 diabetes-free individuals were examined. Single nucleotide polymorphisms of endothelial nitric oxide synthase, 8-oxoguanine DNA glycosylase, and p53 protein, as well as their combinations of polymorphic genes, were tested.

Results. The occurrence rate of the above polymorphic genes in patients with newly diagnosed type 2 diabetes mellitus is close to that in non-diabetic subjects. The most common gene combinations in patients with type 2 diabetes mellitus and the respective controls have been identified. The polygenomic nature of type 2 diabetes mellitus necessitates considering all possible combinations of polymorphic genes.

Conclusion. The results substantiate the need to identify combinations of polymorphisms in patients with newly diagnosed type 2 diabetes mellitus in order to personalize drug therapy and increase its efficacy.

1. Kononenko I.V., Mayorov A.Y., Koksharova E.O., Shestakova M.V. Pharmacogenetics of hypoglycemic agents. Diabetes Mellitus 2015; 18(4): 28–34, https://doi.org/10.14341/dm7681.
2. Staiger H., Schaeffeler E., Schwab M., Häring H.-U. Pharmacogenetics: implications for modern type 2 diabetes therapy. Rev Diabet Stud 2015; 12(3–4): 363–376, https://doi.org/10.1900/rds.2015.12.363.
3. Banerjee M., Vats P. Reactive metabolites and antioxidant gene polymorphisms in type 2 diabetes mellitus. Br J Biomed Sci 2014; 20(1): 10, https://doi.org/10.4103/0971-6866.132747.
4. Fortis M.F., Fraga L.R., Boquett J.A., Kowalski T.W., Dutra C.G., Gonçalves R.O., Vianna F.S.L., Schüler-Faccini L., Sanseverino M.T.V. Angiogenesis and oxidative stress-related gene variants in recurrent pregnancy loss. Reprod Fertil Dev 2018; 30(3): 498–506, https://doi.org/10.1071/rd17117.
5. Seidlerová J., Filipovský J., Mayer O. Jr., Kučerová A., Pešta M. Association between endothelial NO synthase polymorphisms and arterial properties in the general population. Nitric Oxide 2015; 44: 47–51, https://doi.org/10.1016/j.niox.2014.11.016.
6. Miranda J.A., Belo V.A., Souza-Costa D.C., Lanna C.M., Tanus-Santos J.E. eNOS polymorphism associated with metabolic syndrome in children and adolescents. Mol Cell Biochem 2013; 372(1–2): 155–160, https://doi.org/10.1007/s11010-012-1456-y.
7. Torres-Gonzalez M., Gawlowski T., Kocalis H., Scott B.T., Dillmann W.H. Mitochondrial 8-oxoguanine glycosylase decreases mitochondrial fragmentation and improves mitochondrial function in H9C2 cells under oxidative stress conditions. Am J Physiol Cell Physiol 2014; 306(3): C221–C229, https://doi.org/10.1152/ajpcell.00140.2013.
8. Yuzefovych L.V., Solodushko V.A., Wilson G.L., Rachek L.I. Protection from palmitate-induced mitochondrial DNA damage prevents from mitochondrial oxidative stress, mitochondrial dysfunction, apoptosis, and impaired insulin signaling in rat L6 skeletal muscle cells. Endocrinology 2012; 153(1): 92–100, https://doi.org/10.1210/en.2011-1442.
9. Milić M., Kišan M., Rogulj D., Radman M., Lovrenčić M.V., Konjevoda P., Domijan A.M. Level of primary DNA damage in the early stage of metabolic syndrome. Mutat Res 2013; 758(1–2): 1–5, https://doi.org/10.1016/j.mrgentox.2013.07.013.
10. Hara M., Nakamura K., Nanri H., Nishida Y., Hishida A., Kawai S., Hamajima N., Kita Y., Suzuki S., Mantjoro E.M., Ohnaka K., Uemura H., Matsui D., Oze I., Mikami H., Kubo M., Tanaka H.; Japan Multi-Institutional Collaborative Cohort (J-MICC) Study Group. Associations between hOGG1 Ser326Cys polymorphism and increased body mass index and fasting glucose level in the Japanese general population. J Epidemiol 2014; 24(5): 379–384, https://doi.org/10.2188/jea.je20140002.
11. Zhang Z., Tang P. Genomic pathology and biomarkers in breast cancer. Crit Rev Oncog 2017; 22(5–6): 411–426, https://doi.org/10.1615/critrevoncog.v22.i5-6.60.
12. Bonfigli A.R., Sirolla C., Testa R., Cucchi M., Spazzafumo L., Salvioli S., Ceriello A., Olivieri F., Festa R., Procopio A.D., Brandoni G., Boemi M., Marra M., Franceschi C. The p53 codon 72 (Arg72Pro) polymorphism is associated with the degree of insulin resistance in type 2 diabetic subjects: a cross-sectional study. Acta Diabetol 2012; 50(3): 429–436, https://doi.org/10.1007/s00592-012-0450-x.
13. Murk W., DeWan A.T. Exhaustive genome-wide search for SNP-SNP interactions across 10 human diseases. G3 (Bethesda) 2016; 6(7): 2043–2050, https://doi.org/10.1534/g3.116.028563.
14. Tornovsky-Babeay S., Dadon D., Ziv O., Tzipilevich E., Kadosh T., Schyr-Ben Haroush R., Hija A., Stolovich-Rain M., Furth-Lavi J., Granot Z., Porat S., Philipson L.H., Herold K.C., Bhatti T.R., Stanley C., Ashcroft F.M., In’t Veld P., Saada A., Magnuson M.A., Glaser B., Dor Y. Type 2 diabetes and congenital hyperinsulinism cause DNA double-strand breaks and p53 activity in β cells. Cell Metab 2014; 19(1): 109–121, https://doi.org/10.1016/j.cmet.2013.11.007.
15. Rebrova O.Yu. Statisticheskiy analiz meditsinskikh dannykh. Primenenie paketa prikladnykh programm STATISTICA [Statistical analysis of medical data. Application of the software package STATISTICA]. Moscow: MediaSfera; 2006; 312 p.
16. Strycharz J., Drzewoski J., Szemraj J., Sliwinska A. Is p53 involved in tissue-specific insulin resistance formation? Oxid Med Cell Longev 2017; 2017: 1–23, https://doi.org/10.1155/2017/9270549.
17. Kung C.-P., Murphy M.E. The role of the p53 tumor suppressor in metabolism and diabetes. J Endocrinol 2016; 231(2): R61–R75, https://doi.org/10.1530/joe-16-0324.
18. Sorokina Y.A. Pharmacogenetic aspects of oral hypoglycemic therapy. Response and failure phenotypes. Meditsinskiy sovet 2015; 8: 82–85.
19. Sorokina Yu.A., Zanozina O.V., Lovtsova L.V., Seropyan M.Yu. A method of flow prediction efficiency and therapy of patients with type 2 diabetes. Patent RU 2626670. 2017.
20. Urakov A., Urakova N. Rheology and physical-chemical characteristics of the solutions of the medicines. Journal of Physics: Conference Series 2015; 602: 012043, https://doi.org/10.1088/1742-6596/602/1/012043.

Sorokina Yu.A., Lovtsova L.V., Urakov A.L., Zanozina O.V. Genetic Polymorphism in Patients with Newly Diagnosed Type 2 Diabetes Mellitus. Sovremennye tehnologii v medicine 2019; 11(2): 57, https://doi.org/10.17691/stm2019.11.2.08