Role of polymorphisms and microRNA levels in predicting cardiovascular events in patients with acute myocardial infarction

Table 1 Diagnostic value of circulating microRNA levels in acute myocardial infarction

Ref.	Patients (n)	miRNA			Standard	AUC	95%CI	P value
Zhang et al[28], 2015	110 AMI	miRNA-486			Quantitative real-time PCR	0.731	-	< 0.001
		miRNA-150				0.678	-	< 0.001
		miRNA-486 miRNA-150				0.771	-	< 0.001
Peng et al[29], 2014	186 AMI	miRNA -133			Quantitative reverse transcriptase-PCR	0.912	-	< 0.001
		miRNA-1291				0.695		< 0.001
		miRNA-663b				0.611		< 0.01
Wang et al[30], 2014	45 AMI	miRNA-361-5p		0 hours	Quantitative real-time PCR	0.881	0.777–0.985	< 0.001
				4 hours		0.883	0.777–0.989	< 0.001
				24 hours		0.838	0.716–0.961	< 0.001
		miRNA-21-5p		0 hour		0.949	0.872–1.000	< 0.001
				4 hours		0.947	0.000–1.000	< 0.001
				24 hours		0.791	0.655–0.927	0.001
		miRNA-519e-5p		0 hours		0.798	0.663–0.934	0.001
				4 hours		0.801	0.668–0.934	0.002
				24 hours		0.908	0.818–0.997	< 0.001
		Combined score		0 hour		0.989	0.000–1.000	< 0.001
				4 hours		1.000	0.000–1.000	< 0.001
				24 hours		0.995	0.000–1.000	< 0.001
Zhao et al[31], 2023	183 ACS	miRNA-483-5p			Quantitative reverse transcriptase-PCR	0.919	0.881-0.957	-
	78 AMI					0.867	0.800-0.933	-
Xue et al[32], 2019	31 AMI	miRNA-26a-1	Pre-PCI		Quantitative real-time PCR	0.965	-	< 0.001
			Post-PCI			0.939	-	< 0.001
		miRNA-146a	Pre-PCI			0.911	-	< 0.001
			Post-PCI			0.932	-	< 0.001
		miRNA-199a-1	Pre-PCI			0.855	-	< 0.001
			Post-PCI			0.823	-	< 0.001
		Combined	Pre-PCI			0.913	-	< 0.001
			Post-PCI			0.890	-	< 0.001

ACS: Acute coronary syndrome; AMI: Acute myocardial infarction; AUC: Area under the curve; CI: Confidence interval; PCI: Percutaneous coronary intervention.

Table 2 Prognostic value of microRNA levels in predicting post-acute myocardial infarction major adverse cardiovascular events

Ref.	Patients, (n)	miRNA	Follow-up period in months	Standard	Cut off (%)	HR (95%CI)	P value
Xiao et al[27], 2021	192 AMI	miRNA-146a	40	Quantitative real-time PCR	-	1.329 (1.060–1.664)	0.01
Alavi-Moghaddam et al[35], 2018	21 AMI	miRNA-208b	6	Quantitative real-time PCR	12.38	5.08 (1.13–22.82)	0.03
Zhao et al[31], 2023	183 ACS	miRNA-483-5p	6	Quantitative reverse transcriptase-PCR	-	5.955 (1.928-18.389)	0.002

ACS: Acute coronary syndrome; AMI: Acute myocardial infarction; HR: Hazard ratio.

Table 3 Prognostic value of microRNA polymorphism in predicting post-acute myocardial infarction major adverse cardiovascular events

Ref.	Patients (n)	Genetic models	Analyzed model	Population-follow-up period	Standard	HR (95%CI)	P value
Qiao et al[40], 2023	612 ACS	miRNA-146a, rs2910164	Dominant (CC vs CG + GG)	42 months screening for MACE	ABI PRISM3730 DNA Sequencer	1.405 (1.018-1.939)	0.038
			Recessive (CC + CG vs GG)			1.107 (0.821–1.492)	0.506
Li et al[44], 2015	1004 CAD	miRNA-146a, rs2910164	Dominant (CC vs CG + GG)	5 years screening for MACE	PCR-based method	1.119 (0.848-1.478)	0.427
			Recessive (CC + CG vs GG)			1.095 (0.787-1.524)	0.591
			Dominant (CC vs CG + GG)	5 years screening for mortality		0.762 (0.485-1.197)	0.396
			Recessive (CC + CG vs GG)			0.757 (0.398-1.439)	0.203

ABI: Applied Biosystems, Inc; ACS: Acute coronary syndrome; CI: Confidence interval; HR: Hazard ratio; MACE: Major adverse cardiovascular events; miRNA: MicroRNA.

Table 4 Summary of diagnostic and prognostic roles of circulating microRNAs and single nucleotide polymorphisms in acute myocardial infarction

miRNA/SNP	Biological function	AMI diagnostic value	MACE prognostic value	Associated pathway
miR-150	Anti-apoptotic, anti-fibrotic	AUC 0.678–0.771[28]	Predictor of mortality, LV remodeling[18]	SRF, c-Myb, apoptosis
miR-208b	Cardiac-specific, involved in muscle gene regulation	AUC > 0.9 within 3–6 hours[19]	HR = 5.08 for MACE at 6 months[35]	Myocardial contractility genes
miR-483-5p	Inflammation-related	AUC = 0.867–0.919[31]	HR = 5.955 for MACE[31]	NF-κB, cytokines
miR-146a	Regulates IRAK1/TRAF6	AUC = 0.91[32]	HR = 2.712 for MACE[8]	NF-κB, IL-1R/TLR
SNP rs2910164 (miR-146a)	Alters miRNA processing, G/C substitution	↑Risk of AMI[38,40]	HR = 1.405 for MACE (dominant model)[57]	Inflammatory amplification
SNP rs11614913 (miR-196a2)	Influences mature miRNA levels	Associated with severe CAD[39]	HR = 2.44 (recessive model)[58]	Vascular remodeling, SIRT1 signaling
SNP rs3746444 (miR-499)	Affects cardiac muscle gene regulation	Predictor of MI susceptibility[58]	HR = 2.05 for MACE (recessive model)[58]	Myocardial apoptosis and necrosis

AUC: Area under the curve; CAD: Coronary artery disease; HR: Hazard ratio; IL-1R: Interleukin-1 receptor; LV: Left ventricular; MACE: Major adverse cardiovascular events; MI: Myocardial infarction; miRNA: MicroRNA; NF-κB: Nuclear factor-kappa B; SNP: Single nucleotide polymorphism; TLR: Toll-like receptor; TRAF6: Tumor necrosis factor receptor-associated factor 6.

Table 5 Diagnostic value of microRNA polymorphisms in acute myocardial infarction

Ref.	Patients, n	miRNA	Analyzed model	Standard	OR (95%CI)	P value
Wang et al[55], 2017	353 CAD	microRNA-146a, rs2431697	T allele carriers	MALDI-TOF MS, Sequenom MassARRAY system	1.26 (1.04-1.53)	0.018
		microRNA-146a, rs2910164	G allele carriers		0.73 (0.62-0.86)	< 0.001
Tie et al[56], 2023	151 CAD	microRNA-146a, rs2910164	Dominant (CG + GG vs CC)	Real-time PCR	1.59 (0.76–2.81)	0.014
			Recessive (CC vs TT + TC)		0.91 (0.53–2.04)	0.320
		miRNA-146a, rs41291957	Dominant (AA + GA vs GG)		0.71 (0.53–1.35)	0.680
			Recessive (AA vs GG + GA)		0.66 (0.21–1.12)	0.17
Agiannitopoulos et al[58], 2020	80 MI	miRNA-146a, rs2910164	Dominant (CC + CG vs GG)	PCR-RFLP, HRM, Sanger Sequencing	0.97 (0.57-1.63)	1.000
			Recessive (CG + GG vs CC)		1.37 (0.55-3.37)	0.478
		miRNA-149a, rs2292832	Dominant (CT + TT vs CC)		1.03 (0.61-1.74)	1.000
			Recessive (CC + CT vs TT)		1.18 (0.56-2.47)	0.700
		miRNA-196aC, rs11614913	Dominant (CT + TT vs CC)		1.73 (1.02-2.92)	0.047
			Recessive (CC + CT vs TT)		2.44 (1.13-5.27)	0.031
		miRNA-499, rs3746444	Dominant (AG + GG vs AA)		1.87 (1.08-3.24)	0.031
			Recessive (AA + AG vs GG)		2.05 (1.07-3.90)	0.035
Huang et al[42], 2015	718 ACS	miRNA-146a, rs11614913	Dominant (TC + CC vs TT)	Real time quantitative PCR system	1.10 (0.84-1.44)	0.488
			Recessive (CC vs TT + TC)		1.00	-
	717 ACS	miRNA-146a, rs2910164	Dominant (CG + GG vs CC)		0.77 (0.60-0.99)	0.044
			Recessive (CC + CG vs GG)		1.07 (0.79-1.45)	0.673
Zhao et al[59], 2019	5202 CHD	miRNA-146a, rs2910164	Dominant (CC vs CG + GG)	Systematic review	0.8 (0.73–0.87)	< 0.001
			Recessive (CC + CG vs GG)		0.86 (0.76-0.98)	< 0.001

CAD: Coronary artery disease; CHD: Congenital heart disease; CI: Confidence interval; HRM: High-resolution melting analysis; MALDI-TOF MS: Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry; MI: Myocardial infarction; OR: Odds ratio; RFLP: Restriction fragment length polymerase.