ASSOCIATION BETWEEN MALAT1 RS4102217-POLYMORPHIC VARIANT AND ISHEMIC ATHEROTHROMBOTIC STROKE DEVELOPMENT IN PEOPLE WITH INCREASED BODY MASS INDEX

  • Karina A. Moiseіenko Department of Physiology and Pathophysiology with a Medical Biology course, Medical Institute of SSU, Sumy, Ukraine
  • Victoriia Yu. Harbuzova Department of Physiology and Pathophysiology with a Medical Biology course, Medical Institute of SSU, Sumy, Ukraine https://orcid.org/0000-0001-7183-6997
  • Olha A. Obukhova Department of Physiology and Pathophysiology with a Medical Biology course, Medical Institute of SSU, Sumy, Ukraine https://orcid.org/0000-0002-2104-8412
Keywords: SNP, ischemic atherothrombotic stroke, MALAT1, Polymerase chain reaction, long non-coding RNA

Abstract

Background. The recent discovery of a group of mediators known as long non-coding RNAs (lncRNAs) is the basis for research that will reduce the risk of cardiovascular disease in the long run. lncRNAs are expressed depending on conditions, and there is ample evidence of their involvement in a variety of biological processes. Indeed, lncRNA abnormalities are directly related to human diseases, including cardiovascular pathology and other diseases. LncRNA MALAT1 is one of the numerous factors causing functional changes in ischemic atherothrombotic stroke (IATS), in particular, it affects the functioning of endothelial cells and is involved in the implementation of inflammatory processes and regulation of autophagy. All those conditions play a role in the development of atherosclerosis, which underlies the pathogenesis of IATS. The effects of rs4102217-polimorphism of MALAT1 on IATS were poorly explored. This research aimed to find out, whether MALAT1 was associated with the susceptibility to IATS in patients with overweight.

Materials and Methods. A total of 200 ischemic atherothrombotic stroke patients and 234 controls without acute cardiovascular pathology were enrolled in this study. The rs4102217-polymorphisms in the promoter of MALAT1 were genotyped by using Real-Time PCR. Calculations were made using Statistical Package for the Social Sciences software (SPSS, version 17.0). A value of P ˂ 0.05 was considered as statistically significant.

Results. The SNP rs4102217 in the promoter of MALAT1 was associated with the risk of ischemic atherothrombotic stroke in people with increased body mass index (BMI ≥ 25 kg/m2) (Dominant model: adjusted OR = 1.66, 95% CI, 1,024–2,700, P = 0.040)

Conclusions. The results showed that c-carriers with elevated BMI were 1.66 times more likely to develop ischemic atherothrombotic stroke.

References

1. Uchida S, Dimmeler S. Long noncoding RNAs in cardiovascular diseases. Circ Res. 2015;116(4):737-750. doi:10.1161/CIRCRESAHA.116.302521
2. Yan Y, Song D, Song X, Song C. The role of lncRNA MALAT1 in cardiovascular disease. IUBMB Life. 2020;72(3):334-342. doi:10.1002/iub.2210
3. Huang Y. The novel regulatory role of lncRNA-miRNA-mRNA axis in cardiovascular diseases. J Cell Mol Med. 2018;22(12):5768-5775. doi:10.1111/jcmm.13866
4. Bao MH, Szeto V, Yang BB, Zhu SZ, Sun HS, Feng ZP. Long non-coding RNAs in ischemic stroke. Cell Death Dis. 2018;9(3):281. Published 2018 Feb 15. doi:10.1038/s41419-018-0282-x
5. Michalik KM, You X, Manavski Y, et al. Long noncoding RNA MALAT1 regulates endothelial cell function and vessel growth. Circ Res. 2014;114(9):1389-1397. doi:10.1161/CIRCRESAHA.114.303265
6. Tang Y, Jin X, Xiang Y, et al. The lncRNA MALAT1 protects the endothelium against ox-LDL-induced dysfunction via upregulating the expression of the miR-22-3p target genes CXCR2 and AKT. FEBS Lett. 2015;589(20 Pt B):3189-3196. doi:10.1016/j.febslet.2015.08.046
7. Zhao J, Li L, Peng L. MAPK1 up-regulates the expression of MALAT1 to promote the proliferation of cardiomyocytes through PI3K/AKT signaling pathway. Int J Clin Exp Pathol. 2015;8(12):15947-15953. Published 2015 Dec 1.
8. Zhang J, Yuan L, Zhang X, et al. Altered long non-coding RNA transcriptomic profiles in brain microvascular endothelium after cerebral ischemia. Exp Neurol. 2016;277:162-170. doi:10.1016/j.expneurol.2015.12.014
9. Su Y, Zhang L, Zhou Y, Ding L, Li L, Wang Z. The progress of research on histone methylation in ischemic stroke pathogenesis. J Physiol Biochem. 2022;78(1):1-8. doi:10.1007/s13105-021-00841-w
10. Fu S, Wang Y, Li H, Chen L, Liu Q. Regulatory Networks of LncRNA MALAT-1 in Cancer. Cancer Manag Res. 2020;12:10181-10198. Published 2020 Oct 15. doi:10.2147/CMAR.S276022
11. Liang T, Xu F, Wan P, et al. Malat-1 expression in bladder carcinoma tissues and its clinical significance. Am J Transl Res. 2021;13(4):3555-3560. Published 2021 Apr 15.
12. Goyal B, Yadav SRM, Awasthee N, Gupta S, Kunnumakkara AB, Gupta SC. Diagnostic, prognostic, and therapeutic significance of long non-coding RNA MALAT1 in cancer. Biochim Biophys Acta Rev Cancer. 2021;1875(2):188502. doi:10.1016/j.bbcan.2021.188502
13. Mao YM, He YS, Wu GC, et al. Association of MALAT-1 gene single nucleotide polymorphisms with genetic susceptibility to systemic lupus erythematosus. Lupus. 2021;30(12):1923-1930. doi:10.1177/09612033211040366
14. Hu W, Ding H, Ouyang A, et al. LncRNA MALAT1 gene polymorphisms in coronary artery disease: a case-control study in a Chinese population. Biosci Rep. 2019;39(3): BSR20182213. Published 2019 Mar 19. doi:10.1042/BSR20182213
15. Zhang X, Hamblin MH, Yin KJ. The long noncoding RNA Malat1: Its physiological and pathophysiological functions. RNA Biol. 2017;14(12):1705-1714. doi:10.1080/15476286.2017.1358347
16. Wang Y, Gu XX, Huang HT, Liu CH, Wei YS. A genetic variant in the promoter of lncRNA MALAT1 is related to susceptibility of ischemic stroke. Lipids Health Dis. 2020;19(1):57. Published 2020 Apr 1. doi:10.1186/s12944-020-01236-4
17. Gao Q, Wang Y. Long noncoding RNA MALAT1 regulates apoptosis in ischemic stroke by sponging miR-205-3p and modulating PTEN expression. Am J Transl Res. 2020;12(6):2738-2748. Published 2020 Jun 15.
18. Fathy N, Kortam MA, Shaker OG, Sayed NH. Long Noncoding RNAs MALAT1 and ANRIL Gene Variants and the Risk of Cerebral Ischemic Stroke: An Association Study. ACS Chem Neurosci. 2021;12(8):1351-1362. doi: 10.1021/acschemneuro.0c00822
Published
2022-06-30
How to Cite
Karina A. Moiseіenko, Victoriia Yu. Harbuzova, & Olha A. Obukhova. (2022). ASSOCIATION BETWEEN MALAT1 RS4102217-POLYMORPHIC VARIANT AND ISHEMIC ATHEROTHROMBOTIC STROKE DEVELOPMENT IN PEOPLE WITH INCREASED BODY MASS INDEX. Eastern Ukrainian Medical Journal, 10(2), 131-137. https://doi.org/10.21272/eumj.2022;10(2):131-137