Online ISSN: 3007-0244,
Print ISSN:  2410-4280
THE ROLE OF SNCA GENE POLYMORPHISMS IN THE DEVELOPMENT OF CARDIAC AUTONOMIC NEUROPATHY IN INDIVIDUALS OF KAZAKH ETHNICITY
Cardiac autonomic neuropathy (CAN) occurs as a result of cardiac innervation impairment and leads to an increased risk of cardiovascular morbidity and mortality. There is evidence suggesting that alpha-synuclein protein (SNCA) plays a significant role in the pathogenesis of cardiac autonomic neuropathy, particularly in relation to heart rate variability, a major clinical manifestation. The aim of this study was to investigate the association between two SNCA gene polymorphisms (rs2736990 and rs2737029) and cardiac autonomic neuropathy in the Kazakh population. Materials and methods: A case-control study included 82 patients with cardiac autonomic neuropathy, including those with a diabetic etiology (case group), and 100 individuals without a diagnosis of cardiac autonomic neuropathy (control group). All participants were of Kazakh ethnicity. Two SNCA gene polymorphisms, rs2736990 and rs2737029, were investigated. Statistical analysis was performed using chi-square tests, odds ratio calculations with confidence intervals, and logistic regression (SPSS 26.0). Results: Among the two SNCA gene polymorphisms studied, only rs2737029 was associated with cardiac autonomic neuropathy. According to our findings, in a recessive model, the CC genotype increased the odds of having cardiac autonomic neuropathy by almost 2 times (1.93 (1.06-3.53)). After adjusting for age and sex, the results remained significant. However, the association between rs2736990 polymorphism and cardiac autonomic neuropathy did not show statistical significance in any of the models (1.00 (0.63-1.59)). Conclusions: Thus, the presence of the CC genotype of rs2737029 polymorphism in the SNCA gene may be a predisposing factor for the development of cardiac autonomic neuropathy, including the diabetic form. However, the rs2736990 polymorphism in the same gene is not associated with it.
Nazira B. Bekenova1, Alisher D. Aitkaliev1, Ainur S. Sibagatova1, Serik R. Alibekov1, Balzhan S. Kassiyeva1 1 Gerontology Center, Medical Centre Hospital of President’s Affairs Administration, Astana, Republic of Kazakhstan.
1. Коценко Ю., Статинова Е. Современное представление об этиопатогенезе неврологических нарушений при сахарном диабете // Университетская клиника, 2016. 12(2), 76-82. 2. Махинов К.А., Вуйцик Н.Б., Баринов А.Н. Современные аспекты диагностики и лечения нейродегенеративных заболеваний: выявление вегетативных нарушений методом сонографии блуждающего нерва // Opinion Leader. 2020. 12, 50-57. 3. Пчелина С.Н. Альфа-синуклеин как биомаркер болезни Паркинсона // Анналы клинической и экспериментальной неврологии, 2011. 5(4), 46-51. 4. Agashe S., Petak S. Cardiac autonomic neuropathy in diabetes mellitus // Methodist DeBakey cardiovascular journal, 2018. 14(4), 251. 5. Amino T., Orimo S., Itoh Y., Takahashi A., Uchihara T., Mizusawa H. Profound cardiac sympathetic denervation occurs in Parkinson disease // Brain Pathology, 2005. 15(1), 29-34. 6. Angyan L. Role of the substantia nigra in the behavioural-cardiovascular integration in the cat // Acta Physiologica Hungarica, 1989. 74(2), 175-187. 7. Balcıoglu A.S., Müderrisoglu H. Diabetes and cardiac autonomic neuropathy: clinical manifestations, cardiovascular consequences, diagnosis and treatment // World journal of diabetes, 2015. 6(1), 80. 8. Carmona-Abellan M., Gabilondo I., Murueta-Goyena A., Khurana V., Tijero B., Luquin M. R., Acera M., Del Pino R., Gardeazabal J., Martínez-Valbuena I. Small fiber neuropathy and phosphorylated alpha-synuclein in the skin of E46K-SNCA mutation carriers // Parkinsonism & Related Disorders, 2019. 65, 139-145. 9. Ciccacci C., Latini A., Greco C., Politi C., D'Amato C., Lauro D., Novelli G., Borgiani P., Spallone V. Association between a MIR499A polymorphism and diabetic neuropathy in type 2 diabetes // Journal of Diabetes and its Complications, 2018. 32(1), 11-17. 10. Ciccacci C., Morganti R., Di Fusco D., D’Amato C., Cacciotti L., Greco C., Rufini S., Novelli G., Sangiuolo F., Marfia G.A. Common polymorphisms in MIR146a, MIR128a and MIR27a genes contribute to neuropathy susceptibility in type 2 diabetes // Acta Diabetologica, 2014. 51, 663-671. 11. Diabetes Control, & Group C.T.R. The effect of intensive diabetes therapy on measures of autonomic nervous system function in the Diabetes Control and Complications Trial (DCCT) // Diabetologia, 1998. 41(4), 416-423. 12. Dimitropoulos G., Tahrani A.A., Stevens M.J. Cardiac autonomic neuropathy in patients with diabetes mellitus // World journal of diabetes, 2014. 5(1), 17. 13. Dimova R., Tankova T., Guergueltcheva V., Tournev I., Chakarova N., Grozeva G., Dakovska L. Risk factors for autonomic and somatic nerve dysfunction in different stages of glucose tolerance // Journal of Diabetes and its Complications, 2017. 31(3), 537-543. 14. Egonzalez-Reyes R., Aliev G., Avila-Rodrigues M., Barreto E.G. Alterations in glucose metabolism on cognition: a possible link between diabetes and dementia // Current pharmaceutical design, 2016. 22(7), 812-818. 15. Eleftheriadou A., Williams S., Nevitt S., Brown E., Roylance R., Wilding J.P., Cuthbertson D.J., Alam U. The prevalence of cardiac autonomic neuropathy in prediabetes: a systematic review // Diabetologia, 2021. 64, 288-303. 16. Ewing D., Campbell I., Clarke B. Assessment of cardiovascular effects in diabetic autonomic neuropathy and prognostic implications // Annals of Internal Medicine, 1980. 92(2_Part_2), 308-311. 17. Guo X.Y., Chen Y.P., Song W., Zhao B., Cao B., Wei Q.Q., Ou R.W., Yang Y., Yuan L.X., Shang H.F.. SNCA variants rs2736990 and rs356220 as risk factors for Parkinson’s disease but not for amyotrophic lateral sclerosis and multiple system atrophy in a Chinese population // Neurobiology of Aging, 2014. 35(12), 2882. e2881-2882. e2886. 18. Jost W.H. Autonomic dysfunctions in idiopathic Parkinson's disease // Journal of neurology, 2003. 250, i28-i30. 19. Mata I.F., Shi M., Agarwal P., Chung K.A., Edwards K.L., Factor S.A., Galasko D.R., Ginghina C., Griffith A., Higgins D.S. SNCA variant associated with Parkinson disease and plasma α-synuclein level // Archives of neurology, 2010. 67(11), 1350-1356. 20. Meng L., Dunckley E.D., Xu X. Effects of a single dose levodopa on heart rate variability in Parkinson's disease // Zhonghua yi xue za zhi, 2015. 95(7), 493-495. 21. Nemani V.M., Lu W., Berge V., Nakamura K., Onoa B., Lee M.K., Chaudhry F.A., Nicoll R.A., Edwards R.H. Increased expression of α-synuclein reduces neurotransmitter release by inhibiting synaptic vesicle reclustering after endocytosis // Neuron, 2010. 65(1), 66-79. 22. Organization W.H. Obesity and overweight. 9 June 2021. https://www.who.int/en/news-room/fact-sheets/detail/obesity-and-overweight (дата обращения 02.09. 2021). 23. Pop-Busui R., Boulton A.J., Feldman E.L., Bril V., Freeman R., Malik R.A., Sosenko J.M., Ziegler D. Diabetic neuropathy: a position statement by the American Diabetes Association // Diabetes care, 2017. 40(1), 136. 24. Pop-Busui R., Evans G.W., Gerstein H.C., Fonseca V., Fleg J.L., Hoogwerf B.J., Genuth S., Grimm R.H., Corson M.A., Prineas R. Effects of cardiac autonomic dysfunction on mortality risk in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial // Diabetes care, 2010. 33(7), 1578-1584. 25. Spallone V. Update on the impact, diagnosis and management of cardiovascular autonomic neuropathy in diabetes: what is defined, what is new, and what is unmet // Diabetes & metabolism journal, 2019. 43(1), 3-30. 26. Spallone V., Ziegler D., Freeman R., Bernardi L., Frontoni S., Pop‐Busui R., Stevens M., Kempler P., Hilsted J., Tesfaye S. Cardiovascular autonomic neuropathy in diabetes: clinical impact, assessment, diagnosis, and management // Diabetes/metabolism research and reviews, 2011. 27(7), 639-653. 27. Stuckey M.I., Tulppo M.P., Kiviniemi A.M., Petrella R.J. Heart rate variability and the metabolic syndrome: a systematic review of the literature // Diabetes/metabolism research and reviews, 2014. 30(8), 784-793. 28. Svensson M.K., Lindmark S., Wiklund U., Rask P., Karlsson M., Myrin J., Kullberg J., Johansson L., Eriksson J.W. Alterations in heart rate variability during everyday life are linked to insulin resistance. A role of dominating sympathetic over parasympathetic nerve activity? // Cardiovascular diabetology, 2016. 15, 1-9. 29. Tannus L., Drummond K., Clemente E., da Matta Mde F., Gomes M. Predictors of cardiovascular autonomic neuropathy in patients with type 1 diabetes // Front Endocrinol (Lausanne) 2014. 5: 191. In. 30. Tesfaye S., Boulton A.J., Dyck P.J., Freeman R., Horowitz M., Kempler P., Lauria G., Malik R. A., Spallone V., Vinik A. Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments // Diabetes care, 2010. 33(10), 2285-2293. 31. Thorp A. A., Schlaich M.P. Relevance of sympathetic nervous system activation in obesity and metabolic syndrome. Journal of diabetes research, 2015. 15, 1-12. 32. Vinik A.I., Erbas T., Casellini C.M. Diabetic cardiac autonomic neuropathy, inflammation and cardiovascular disease // Journal of diabetes investigation, 2013. 4(1), 4-18. 33. Vinik A.I., Maser R.E., Mitchell B.D., Freeman R. Diabetic autonomic neuropathy // Diabetes care, 2003. 26(5), 1553-1579. 34. Vinik A.I., Ziegler D. Diabetic cardiovascular autonomic neuropathy. Circulation, 2007. 115(3), 387-397. 35. Williams S.M., Eleftheriadou A., Alam U., Cuthbertson D.J., Wilding J.P. Cardiac autonomic neuropathy in obesity, the metabolic syndrome and prediabetes: a narrative review // Diabetes Therapy, 2019. 10, 1995-2021. 36. Wulsin L.R., Horn P.S., Perry J.L., Massaro J.M., D'Agostino R.B. Autonomic imbalance as a predictor of metabolic risks, cardiovascular disease, diabetes, and mortality // The Journal of Clinical Endocrinology & Metabolism, 2015. 100(6), 2443-2448. 37. Zhang Y., Shu L., Sun Q., Pan H., Guo J., Tang B. A comprehensive analysis of the association between SNCA polymorphisms and the risk of Parkinson's disease // Frontiers in Molecular Neuroscience, 2018. 11, 391. References: [1-3] 1. Kotsenko Yu., Statinova E. Sovremennoe predstavlenie ob etiopatogeneze nevrologicheskikh narushenii pri sakharnom diabete [Modern views on etiopathogenesis of neurological disorders in diabetes mellitus]. Universitetskaya klinika [University clinic], 2016. 12(2), 76-82. [in Russian] 2. Makhinov K.A., Vuitsik N.B., Barinov A.N. Sovremennye aspekty diagnostiki i lecheniya neirodegenerativnykh zabolevanii: vyyavlenie vegetativnykh narushenii metodom sonografii bluzhdayushchego nerva [Modern aspects of diagnosis and treatment of neurodegenerative diseases: detection of autonomic disorders using sonography of the vagus nerve]. Opinion Leader [Opinion Leader]. 2020. 12, 50-57. [in Russian] 3. Pchelina S.N. Al'fa-sinuklein kak biomarker bolezni Parkinsona [Alpha-synuclein as a biomarker for Parkinson's disease]. Annaly klinicheskoi i eksperimental'noi nevrologii [Annals of Clinical and Experimental Neurology], 2011. 5(4), 46-51. [in Russian]
Number of Views: 412

Key words:

Category of articles: Original articles

Bibliography link

Bekenova N.B., Aitkaliev A.D., Sibagatova A.S., Alibekov S.R., Kassiyeva B.S. The role of SNCA gene polymorphisms in the development of cardiac autonomic neuropathy in individuals of Kazakh ethnicity // Nauka i Zdravookhranenie [Science & Healthcare]. 2023, (Vol.25) 4, pp. 59-66. doi 10.34689/SH.2023.25.4.007

Авторизируйтесь для отправки комментариев