Incidence of MicroR-4513C/T Gene Variability in Coronary Artery Disease - A case-Control Study

Author(s): Rashid Mir*, Chandan k Jha, Imadeldin Elfaki, Jamsheed Javid, Suriya Rehman, Naina Khullar, Shaheena Banu, S. M. S. Chahal*

Journal Name: Endocrine, Metabolic & Immune Disorders - Drug Targets
Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders

Volume 19 , Issue 8 , 2019

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Graphical Abstract:


Background: Genetic variants in pre-microRNA genes or the 3'UTR of miRNA target genes could influence miRNA-mediated regulation of gene expression and thus contribute to the susceptibility and prognosis of human diseases. Several studies have investigated the association of genetic variants in the seed region of miRNAs with cardiometabolic phenotypes .Therefore the aim of study was to investigate the potential association of miR-4513 rs2168518 C>T gene variability with the risk of developing CAD and its association with different cardiometabolic phenotypes in an Indian cohort to stratify CAD burden in the general population.

Methods: The study was conducted on 100 clinically confirmed CAD patients and 100 healthy individuals. Genotyping of MicroR-4513 rs2168518C>T gene variability was performed using Amplification refractory mutation system PCR method.

Results: A significant difference was observed in the genotype distribution among CAD cases and healthy controls. The frequencies of three genotypes CC, CT, TT in CAD patient and healthy controls were 5%, 77%, 18%, and 28%, 45% and 27% respectively. A multivariate analysis showed that miR- 4513 rs2168518 polymorphism is associated with an increased susceptibility to CAD in codominant inheritance model for variant CC vs. CT OR 9.58 CI (3.45-26.57), RR 2.3(1.75-3.02), P=0.001. Results also indicate a potential dominant effect of miR-4513 rs2168518 C/T polymorphism on susceptibility of CAD in dominant inheritance model for variant CC vs. (CT+TT) OR 7.38 (2.71-20.07), RR 1.96 (1.56-2.46), P=0.001. In allelic comparison, T allele weakly increased risk of CAD compared to C allele (OR=1.50, 95% CI (1.09-2.26) RR 1.15 (0.94-1.39) P=0.044.

Conclusion: It is concluded that CT genotype and T allele of microR-4513 rs2168518 is strongly associated with increased susceptibility to CAD. Furthers studies with larger sample sizes are necessary to confirm this result.

Keywords: Coronary artery disease (CAD), microR-rs2168518C/T gene, amplification refractory mutation system PCR method (ARMS-PCR), gene variability, cardiovascular diseases, genetic factors.

Dai, X.; Wiernek, S.; Evans, J.P.; Runge, M.S. Genetics of coronary artery disease and myocardial infarction. World J. Cardiol., 2016, 8(1), 1-23.
[] [PMID: 26839654]
Cassar, A.; Holmes, D.R., Jr; Rihal, C.S.; Gersh, B.J. Chronic coronary artery disease: diagnosis and management. Mayo Clin. Proc., 2009, 84(12), 1130-1146.
[] [PMID: 19955250]
Simon, A.S.; Vijayakumar, T. Molecular studies on coronary artery disease-a review. Indian J. Clin. Biochem., 2013, 28(3), 215-226.
[] [PMID: 24426215]
Wong, N.D. Epidemiological studies of CHD and the evolution of preventive cardiology. Nat. Rev. Cardiol., 2014, 11(5), 276-289.
[] [PMID: 24663092]
Roberts, R. Genetics of coronary artery disease: an update. Methodist DeBakey Cardiovasc. J., 2014, 10(1), 7-12.
[] [PMID: 24932356]
Hajar, R. 2017.
McPherson, R.; Tybjaerg-Hansen, A. Genetics of Coronary Artery Disease. Circ. Res., 2016, 118(4), 564-578.
[] [PMID: 26892958]
Elfaki, I.; Almutairi, F.M.; Mir, R.; Khan, R.; Abu-Duhier, F. Cyto-chrome P450 CYP1B1*2 gene and its Association with T2D in Tabuk Population, Northwestern Region of Saudi Arabia. Asian Journal of Pharmaceutical and Clinical Research, 2018, 11(1), 55-59.
Elfaki, I.; Mir, R.; Almutairi, F.M.; Duhier, F.M.A. Cytochrome P450: Polymorphisms and Roles in Cancer, Diabetes and Atherosclerosis. Asian Pac. J. Cancer Prev., 2018, 19(8), 2057-2070.
[PMID: 30139042]
Macfarlane, L.A.; Murphy, P.R.; Micro, R.N.A. MicroRNA: Biogenesis, Function and Role in Cancer. Curr. Genomics, 2010, 11(7), 537-561.
[] [PMID: 21532838]
Felekkis, K.; Touvana, E.; Stefanou, Ch.; Deltas, C. microRNAs: a newly described class of encoded molecules that play a role in health and disease. Hippokratia, 2010, 14(4), 236-240.
[PMID: 21311629]
Iwakawa, H.O.; Tomari, Y. The Functions of MicroRNAs: mRNA Decay and Translational Repression. Trends Cell Biol., 2015, 25(11), 651-665.
[] [PMID: 26437588]
Nolte-’t Hoen, E.N.; Van Rooij, E.; Bushell, M.; Zhang, C.Y.; Dashwood, R.H.; James, W.P.; Harris, C.; Baltimore, D. The role of microRNA in nutritional control. J. Intern. Med., 2015, 278(2), 99-109.
[] [PMID: 25832550]
Dikeakos, P.; Theodoropoulos, G.; Rizos, S.; Tzanakis, N.; Zografos, G.; Gazouli, M. Association of the miR-146aC>G, miR-149T>C, and miR-196a2T>C polymorphisms with gastric cancer risk and survival in the Greek population. Mol. Biol. Rep., 2014, 41(2), 1075-1080.
[] [PMID: 24379078]
Peng, Y.; Croce, C.M. The role of MicroRNAs in human cancer. Signal Transduct. Target. Ther., 2016, 1, 15004.
[] [PMID: 29263891]
Zou, F.; Li, J.; Jie, X.; Peng, X.; Fan, R.; Wang, M.; Wang, J.; Liu, Z.; Li, H.; Deng, H.; Yang, X.; Luo, D. Rs3842530 Polymorphism in MicroRNA-205 Host Gene in Lung and Breast Cancer Patients. Med. Sci. Monit., 2016, 22, 4555-5464.
[] [PMID: 27885248]
Ghanbari, M.; de Vries, P.S.; de Looper, H.; Peters, M.J.; Schurmann, C.; Yaghootkar, H.; Dörr, M.; Frayling, T.M.; Uitterlinden, A.G.; Hofman, A.; van Meurs, J.B.; Erkeland, S.J.; Franco, O.H.; Dehghan, A. A genetic variant in the seed region of miR-4513 shows pleiotropic effects on lipid and glucose homeostasis, blood pressure, and coronary artery disease. Hum. Mutat., 2014, 35(12), 1524-1531.
[] [PMID: 25256095]
Li, Q.; Chen, L.; Chen, D.; Wu, X.; Chen, M. Influence of microRNA-related polymorphisms on clinical outcomes in coronary artery disease. Am. J. Transl. Res., 2015, 7(2), 393-400.
[PMID: 25901206]
Borghini, A.; Andreassi, M.G. Genetic polymorphisms offer insight into the causal role of microRNA in coronary artery disease. Atherosclerosis, 2018, 269, 63-70.
[] [PMID: 29276984]
Vegter, E.L.; van der Meer, P.; de Windt, L.J.; Pinto, Y.M.; Voors, A.A. MicroRNAs in heart failure: from biomarker to target for therapy. Eur. J. Heart Fail., 2016, 18(5), 457-468.
[] [PMID: 26869172]
Srivastava, K.; Tyagi, K. Single nucleotide polymorphisms of microRNA in cardiovascular diseases., 2018.
Gupta, R.; Mohan, I.; Narula, J. Trends in Coronary Heart Disease Epidemiology in India. Ann. Glob. Health, 2016, 82(2), 307-315.
[] [PMID: 27372534]
Yu, E.; Rimm, E.; Qi, L.; Rexrode, K.; Albert, C.M.; Sun, Q.; Willett, W.C.; Hu, F.B.; Manson, J.E. Diet, Lifestyle, Biomarkers, Genetic Factors, and Risk of Cardiovascular Disease in the Nurses’ Health Studies. Am. J. Public Health, 2016, 106(9), 1616-1623.
[] [PMID: 27459449]
Economou, E.K.; Oikonomou, E.; Siasos, G.; Papageorgiou, N.; Tsalamandris, S.; Mourouzis, K.; Papaioanou, S.; Tousoulis, D. The role of microRNAs in coronary artery disease: From pathophysiology to diagnosis and treatment. Atherosclerosis, 2015, 241(2), 624-633.
[] [PMID: 26117399]
Kwak, P.B.; Iwasaki, S.; Tomari, Y. The microRNA pathway and cancer. Cancer Sci., 2010, 101(11), 2309-2315.
[] [PMID: 20726859]
Heni, M.; Haupt, A.; Schäfer, S.A.; Ketterer, C.; Thamer, C.; Machicao, F.; Stefan, N.; Staiger, H.; Häring, H.U.; Fritsche, A. Association of obesity risk SNPs in PCSK1 with insulin sensitivity and proinsulin conversion. BMC Med. Genet., 2010, 11, 86.
[] [PMID: 20534142]
Pan, S.; Guan, G.C.; Lv, Y.; Liu, Z.W.; Liu, F.Q.; Zhang, Y.; Zhu, S.M.; Zhang, R.H.; Zhao, N.; Shi, S.; Nakayama, T.; Wang, J.K. G-T haplotype established by rs3785889-rs16941382 in GOSR2 gene is associated with coronary artery disease in Chinese Han population. Oncotarget, 2017, 8(47), 82165-82173.
[] [PMID: 29137253]
Pan, S.; Nakayama, T.; Sato, N.; Izumi, Y.; Soma, M.; Aoi, N.; Ma, Y.; Hinohara, S.; Doba, N. A haplotype of the GOSR2 gene is associated with myocardial infarction in Japanese men. Genet. Test. Mol. Biomarkers, 2013, 17(6), 481-488.
[] [PMID: 23675987]

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Article Details

Year: 2019
Published on: 11 November, 2019
Page: [1216 - 1223]
Pages: 8
DOI: 10.2174/1871530319666190417111940
Price: $65

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