Online ISSN: 3007-0244,
Print ISSN:  2410-4280
RELATIONSHIP OF THE rs564398 POLYMORPHISM OF THE ANRIL GENE (CDKN2B) WITH COMPLICATIONS OF TYPE 2 DIABETES, PARTICULARLY WITH THE CARDIOVASCULAR FORM OF DIABETIC NEUROPATHY
Introduction. It is known that cardiovascular diabetic neuropathy or cardiac autonomic neuropathy plays a role in the pathogenesis of vascular damage and subsequent cardiac artery disease, which can lead to disability. Currently, genetic mechanisms in the development of cardiac diabetic neuropathy are of interest. Objective of the study. To evaluate the association of the polymorphisms rs1011970, rs62560775, rs72652411, and rs564398 of the ANRIL gene (CDKN2B) with cardiac autonomic neuropathy to identify genetic markers of cardiovascular complications in diabetic patients of the Kazakh population. Materials and methods. A case-control study included 67 patients with diabetes complicated by cardiovascular diabetic neuropathy and 234 individuals in the control group. The research was conducted at the Medical Center Hospital of the President’s affairs Administration of the Republic of Kazakhstan. Genotyping was performed using real-time PCR. Statistical analysis was conducted using Chi-square methods and odds ratio (OR) calculation with a 95% confidence interval (CI). Statistical calculations were carried out using the Gen Expert genetic calculator. Results. According to the findings, only the polymorphism rs564398 of the ANRIL gene (CDKN2B) was associated with cardiac neuropathy (p=0.03). The C allele and CC genotype predispose to disease (1.72 (1.10-2.69) and 1.89 (1.08 – 3.31), respectively). The remaining polymorphisms rs1011970, rs62560775, and rs72652411 were not associated with the outcome of diabetes in our sample. Conclusions. Thus, the polymorphism rs564398 of the ANRIL gene (CDKN2B) is associated with a predisposition to cardiac autonomic diabetic neuropathy. Further research in this area will help assess its impact on the development of cardiac autonomic neuropathy.
Nazira B. Bekenova1, https://orcid.org/0000-0002-3312-3299 Alisher D. Aitkaliev1, https://orcid.org/0009-0002-9624-2663 Balzhan S. Kassiyeva1, https://orcid.org/0000-0002-8452-7146 Tamara A. Vochshenkova1, https://orcid.org/0000-0003-0935-6217 Akmaral B. Suleimenova1, Valerji V. Benberin1,
1. Abdul Azeez S., Al-Nafie A.N., Al-Shehri A. Intronic Polymorphisms in the CDKN2BAS1 Gene Are Strongly Associated with the Risk of Myocardial Infarction and Coronary Artery Disease in the Saudi Population. Int J Mol Sci. 2016, 17(3), 1-10 2. AlRasheed M.M., Hefnawy M.M. et al. The role of CDKN2B in cardiovascular risk in ethnic Saudi Arabs: a validation study. Gene. 2018, 673, 206-210. 3. Ammar M.N., Lipovich L. et al. Genetic association of rs564398 polymorphism of the ANRIL long non-coding RNA gene and risk of type 2 diabetes: A meta-analysis. Meta Gene. 2022, 31, 1-12. 4. Balcıoğlu A.S., Müderrisoğlu H. Diabetes and cardiac autonomic neuropathy: Clinical manifestations, cardiovascular consequences, diagnosis and treatment. World J Diabetes. 2015, 6(1), 80-91. 5. Bedlack R.S., Edelman D., Gibbs J.W. et al. APOE genotype is a risk factor for neuropathy severity in diabetic patients. Neurology. 2003, 60(6), 1022-1024. 6. Congrains A., Kamide K., Oguro R. et al. Genetic variants at the 9p21 locus contribute to atherosclerosis through modulation of ANRIL and CDKN2A/B. Atherosclerosis. 2012. 220(2), 449-455. 7. Cunnington M.S., Santibanez Koref M., et al. Chromosome 9p21 SNPs associated with multiple disease phenotypes correlate with ANRIL expression. PLoS Genet. 2010. 6(4), 1-17. 8. El-Lebedy D., Raslan H.M., Mohammed A.M. Apolipoprotein E gene polymorphism and risk of type 2 diabetes and cardiovascular disease. Cardiovascular diabetology. 2016. 15, 1-11. 9. Fan M., Dandona S., McPherson R. et al. Two chromosome 9p21 haplotype blocks distinguish between coronary artery disease and myocardial infarction risk. Circulation. Cardiovascular Genetics. 2013. 6(4), 372-80. 10. Foroughmand A.M., Nikkhah E., Galehdari H. et al. Association Study between Coronary Artery Disease and rs1333049 and rs10757274 Polymorphisms at 9p21 Locus in South-West Iran. Cell journal. 2015. 17, 89-98. 11. Glovaci D., Fan W., Wong N.D. Epidemiology of Diabetes Mellitus and Cardiovascular Disease. Curr Cardiol Rep. 2019. 21(4), 1-8. 12. Hannou S.A., Wouters K., Paumelle R., Staels B. Functional genomics of the CDKN2A/B locus in cardiovascular and metabolic disease: what have we learned from GWASs? Trends in Endocrinology & Metabolism. 2015., 26(4), 176-184. 13. Huang G., Liang D., Luo L., Lan C., Luo C., Xu H. Significance of the lncRNAs MALAT1 and ANRIL in occurrence and development of glaucoma. Journal of Clinical Laboratory Analysis. 2022. 36(2), 2421-2425. 14. Iacobucci I., Sazzini M., Garagnani P., Ferrari A., Boattini A., Lonetti A. A polymorphism in the chromosome 9p21 ANRIL locus is associated to Philadelphia positive acute lymphoblastic leukemia. Leukemia research. 2011. 35(8), 1052-1059. 15. Jyotsna V.P., Sahoo A., Sreenivas V., Deepak K. Prevalence and pattern of cardiac autonomic dysfunction in newly detected type 2 diabetes mellitus. Diabetes research and clinical practice. 2009. 83(1), 83-88. 16. Kalinina N., Agrotis A., Antropova Y. et al. Smad expression in human atherosclerotic lesions: evidence for impaired TGF-β/Smad signaling in smooth muscle cells of fibrofatty lesions. Arteriosclerosis, thrombosis, and vascular biology. 2004. 24(8), 1391-1396. 17. Kong Y., Sharma R.B., Nwosu B.U., Alonso L.C. Islet biology, the CDKN2A/B locus and type 2 diabetes risk. Diabetologia. 2016. 59(8), 1579-1593. 18. Mafi Golchin M., Ghaderian S., Akhavan-Niaki H. Analysis of Two CDKN2B-AS Polymorphisms in Relation to Coronary Artery Disease Patients in North of Iran. International journal of molecular and cellular medicine. 2017. 6, 31-37. 19. Mala S., Potockova V., Hoskovcova L. et al. Cardiac autonomic neuropathy may play a role in pathogenesis of atherosclerosis in type 1 diabetes mellitus. Diabetes Res Clin Pract. 2017. 134, 139-144. 20. Monastiriotis C., Papanas N. et al. State of the art paper APOE gene polymorphisms and diabetic peripheral neuropathy. Archives of Medical Science. 2012. 8(4), 583-588. 21. Piya M.K., Shivu G.N. et al. Abnormal left ventricular torsion and cardiac autonomic dysfunction in subjects with type 1 diabetes mellitus. Metabolism. 2011. 60(8), 1115-1121. 22. Pop-Busui R. Cardiac autonomic neuropathy in diabetes: a clinical perspective. Diabetes Care. 2010. 33(2), 434-41. 23. Ram R., Muiya N.P., Mehta M. et al. A genome-wide association study reveals susceptibility loci for myocardial infarction/coronary artery disease in Saudi Arabs. Atherosclerosis 2016. 245, 62-70 24. Serhiyenko V.A., Serhiyenko A.A. Cardiac autonomic neuropathy: Risk factors, diagnosis and treatment. World J Diabetes. 2018. 9(1), 1-24. 25. Shah M.S., Brownlee M. Molecular and Cellular Mechanisms of Cardiovascular Disorders in Diabetes. Circ Res. 2016. 118(11):1808-1829. 26. Shang Y., Zhang X., Leng W., Lei X., Chen L., Zhou X. et al. Increased fractal dimension of left ventricular trabeculations is associated with subclinical diastolic dysfunction in patients with type-2 diabetes mellitus. Int J Cardiovasc Imaging. 2019. 35(4), 665-73. 27. Son J., Accili D. Reversing pancreatic β-cell dedifferentiation in the treatment of type 2 diabetes. Experimental & Molecular Medicine. 2023. 55(8), 1652-1658. 28. Witzel I.I., Jelinek H.F., Khalaf K. et al. Identifying common genetic risk factors of diabetic neuropathies. Front Endocrinol (Lausanne). 2015. 6 (88), 1-18. 29. Yang X., Xu W., Zhu Y. et al. Decreased b-Cell Function is Associated with Cardiovascular Autonomic Neuropathy in Chinese Patients Newly Diagnosed with Type 2 Diabetes. Neuroscience Bulletin. 2018. 35, 25-33. 30. Zhao Y., Zhu R. et al. Genetics of diabetic neuropathy: Systematic review, meta-analysis and trial sequential analysis. Annals of Clinical and Translational Neurology. 2019. 6(10), 1996-2013.
Количество просмотров: 86

Ключевые слова:


Библиографическая ссылка

Bekenova N.B., Aitkaliev A.D., Kassiyeva B.S., Vochshenkova T.A., Suleimenova A.B., Benberin V.V. Relationship of the rs564398 polymorphism of the ANRIL gene (CDKN2B) with complications of type 2 diabetes, particularly with the cardiovascular form of diabetic neuropathy // Nauka i Zdravookhranenie [Science & Healthcare]. 2024. Vol.26 (5), pp. 55-61. doi 10.34689/SH.2024.26.5.007

Авторизируйтесь для отправки комментариев