MicroRNA-224 (rs188519172 A>G) Gene Variability is Associated with a Decreased Susceptibility to Coronary Artery Disease: A Case-Control Study

Author(s): Rashid Mir*, Chandan K. Jha, Imadeldin Elfaki*, Suriya Rehman, Jamsheed Javid, Naina Khullar, Shaheena Banu, Sukh Mohinder Singh Chahal*.

Journal Name: MicroRNA

Volume 8 , Issue 3 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Aim: The microRNAs regulate the expression of multiple genes involved in diseases such as cancer, diabetes and cardiovascular disease. In this study, we have investigated the association between the miR-224 gene polymorphism (rs188519172A>G) and susceptibility of coronary artery disease CAD.

Methodology: Hundred CAD patients and 100-matched healthy control were included. Genotyping of the miR-224 (rs188519172A>G) polymorphism was performed using Amplification refractory mutation system PCR method (ARMS-PCR).

Results: A significant difference was observed in the genotype distribution among CAD patients and healthy controls (P=0.018). The frequencies of all three genotypes GG, GA, AA reported in the patient’s samples were 33%, 66% and 01%, and in the healthy controls samples, were 16%, 82% and 2% respectively. A multivariate analysis based on logistic regression was conducted for each group to estimate the association between miR-224 rs188519172 genotypes and risk to coronary artery disease. Results show that the miR-224 (rs188519172 A>G) polymorphism was associated with a decreased risk to CAD in a codominant model, GA genotype vs. GG (OR = 0.39 (95 % CI, 0.19-0.76), RR 0.58 (0.38-0.90, P=0.006). In the dominant model, (GA+AA vs. GG), there was also a significant association with the OR=0.38 (95 % CI (0.19-0.76), RR 0.58 (0.38-0.89), and P=0.006. Whereas, in the recessive model, (GG+GA vs. AA), there was no significant association of CAD with OR=0.49 (95% CI (0.044-5.54), RR 0.74 (0.33-1.68), and P=0.48.

Conclusion: Our findings indicated that miR-224 (rs188519172) GA genotype is associated with a decreased susceptibility to CAD.

Keywords: Amplification refractory mutation system PCR method (ARMS-PCR), coronary artery disease, Micro-RNA polymorphism, MiR-224 (rs188519172A>G) polymorphism, gene, healthy control.

Nag T, Ghosh A. Cardiovascular disease risk factors in Asian Indian population: a systematic review. J Cardiovasc Dis Res 2013; 4(4): 222-8.
Cannon B. Cardiovascular disease: biochemistry to behaviour. Nature 2013; 493(7434): S2-3.
Wong ND. Epidemiological studies of CHD and the evolution of preventive cardiology. Nat Rev Cardiol 2014; 11(5): 276-89.
Sayols-Baixeras S, Lluis-Ganella C, Lucas G, Elosua R. Pathogenesis of coronary artery disease: focus on genetic risk factors and identification of genetic variants. The Appl Clin Genet 2014; 7: 15-32.
Srivastava K, Tyagi K. Single nucleotide polymorphisms of microRNA in cardiovascular diseases. Clin Chim Acta 2018; 478: 101-10.
Elfaki I, Almutairi FM, Mir R, Khan R, Abu-Duhier F. Cytochrome P450 CYP1B1*2 gene and its association with T2D in Tabuk population, northwestern region of Saudi Arabia. Asian J Pharmaceut Clin Res 2018; 11(1): 55-9.
Elfaki I, Mir R, Almutairi FM, Duhier FMA. Cytochrome P450: polymorphisms and roles in cancer, diabetes and atherosclerosis. Asian Pac J Cancer Prev 2018; 19(8): 2057-70.
Filipowicz W, Bhattacharyya SN, Sonenberg N. Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet 2008; 9(2): 102-14.
Iwakawa HO, Tomari Y. The functions of microRNAs: mRNA decay and translational repression. Trends Cell Biol 2015; 25(11): 651-65.
Nariman-Saleh-Fam Z, Bastami M, Somi MH, et al. miRNA-related polymorphisms in miR-423 (rs6505162) and PEX6 (rs1129186) and risk of esophageal squamous cell carcinoma in an Iranian Cohort. Genet Test Mol Biomarkers 2017; 21(6): 382-90.
Zhang W, Dahlberg JE, Tam W. MicroRNAs in tumorigenesis: a primer. The Am J Pathol 2007; 171(3): 728-38.
Felekkis K, Touvana E, Stefanou C, Deltas C. microRNAs: a newly described class of encoded molecules that play a role in health and disease. Hippokratia 2010; 14(4): 236-40.
Moszynska A, Gebert M, Collawn JF, Bartoszewski R. SNPs in microRNA target sites and their potential role in human disease. Open Biol 2017; 7(4): 170019.
Zorc M, Skok DJ, Godnic I, et al. Catalog of microRNA seed polymorphisms in vertebrates. PLoS One 2012; 7(1): e30737.
Jha CK, Mir R, Elfaki I, et al. Potential impact of microRNA-423 gene variability in coronary artery disease. Endocr Metab Immune Disord Drug Targets 2019; 19(1): 67-74.
Olaru AV, Yamanaka S, Vazquez C, et al. MicroRNA-224 negatively regulates p21 expression during late neoplastic progression in inflammatory bowel disease. Inflamm Bowel Dis 2013; 19(3): 471-80.
Naeli P, Mirzadeh Azad F, Malakootian M, Seidah NG, Mowla SJ. Post-transcriptional regulation of PCSK9 by miR-191, miR-222, and miR-224. Front Genet 2017; 8: 189.
Raal F, Panz V, Immelman A, Pilcher G. Elevated PCSK9 levels in untreated patients with heterozygous or homozygous familial hypercholesterolemia and the response to high-dose statin therapy. J Am Heart Assoc 2013; 2(2): e000028.
Peng Y, Xiang H, Chen C, et al. MiR-224 impairs adipocyte early differentiation and regulates fatty acid metabolism. The Int J Biochem Cell Biol 2013; 45(8): 1585-93.
Chuanyin L, Xiaona W, Zhiling Y, et al. The association between polymorphisms in microRNA genes and cervical cancer in a Chinese Han population. Oncotarget 2017; 8(50): 87914-27.
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.
Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. The New N Engl J Med 2005; 352(16): 1685-95.
Miller CL, Haas U, Diaz R, et al. Coronary heart disease-associated variation in TCF21 disrupts a miR-224 binding site and miRNA-mediated regulation. PLoS Genet 2014; 10(3): e1004263.
Paone C, Diofano F, Park DD, Rottbauer W, Just S. Genetics of cardiovascular disease: fishing for causality. Front Cardiovasc Med 2018; 5: 60.
Maxwell KN, Fisher EA, Breslow JL. Overexpression of PCSK9 accelerates the degradation of the LDLR in a post-endoplasmic reticulum compartment. Proc Natl Acad Sci USA 2005; 102(6): 2069-74.
Hess CN, Low Wang CC, Hiatt WR. PCSK9 inhibitors: mechanisms of action, metabolic effects, and clinical outcomes. Annu Rev Med 2018; 69: 133-45.
Lu MC, Lai NS, Chen HC, et al. Decreased microRNA(miR)-145 and increased miR-224 expression in T cells from patients with systemic lupus erythematosus involved in lupus immunopathogenesis. Clin Exp Immunol 2013; 171(1): 91-9.
Tse K, Tse H, Sidney J, Sette A, Ley K. T cells in atherosclerosis. Int Immunol 2013; 25(11): 615-22.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Page: [198 - 205]
Pages: 8
DOI: 10.2174/2211536608666181211153859
Price: $58

Article Metrics

PDF: 32