The Potential of Single Nucleotide Polymorphisms (SNPs) as Biomarkers and Their Association with the Increased Risk of Coronary Heart Disease: A Systematic Review

Figures & data

Figure 1 Schematic of Selection of Articles from Database with PRISMA Flowchart Method.

Notes: PRISMA figure adapted from Page MJ, McKenzie JE, Bossuyt PM et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. Creative Commons.²⁰

Abbreviations: CHD, Coronary Heart Disease; RCT, Randomized Controlled Trial.

Table 1 Data Extraction Results

SNPs	Genetic Polymorphism	Gene Expression	Clinical Manifestations	Statistical Value	Population			Study Design	Ref
					Sample Size	Characteristics	Country
rs1946519	A>C	IL-18	Increase of inflammation	OR (1.1); 95% CI (0.91–1.43); p (0.11)	650	340 patients with preterm CHD and 310 controls	Pakistan	Case-control study	[47]
rs187238	C>A / C>G	IL-18 IL-6		OR (1.1); 95% CI (1.01–1.43); p (0.015)
rs1800871	A>G	IL-10		OR (1.2); 95% CI (0.81–1.55); p (0.19)
rs1801133	G>A / G>C	MTHFR	Increased homocysteine	OR (1.1); 95% CI (1.09–1.26); p<0.000	504	254 patients and 250 controls	Pakistan	Retrospective case-control association study	[42]
rs1805087	A>G	MTR		OR (1.2); 95% CI (1.14–1.30); p<0.000
rs10127904	T>C,G	CR1	Immune response and pro inflammation	p (0.0489)	5244	70–82 years old	Scotland, Ireland, Netherland	Prospective cohort study	[53]
rs17259038	A>G
rs2457564	G>A	LPA	Changes in apolipoprotein isoform size	OR (0.9); 95% CI (0.98–0.99); p<0.0001	184.305	60,801 samples from CARDioGRAMplusC4D and 123,504 controls	Pakistan	Mendelian randomization study (observational study)	[30]
rs3777392	C>G,T			OR (1.1); 95% CI (1.10–1.14); p<0.0001
rs11591147	G>A,T	PCSK9	Decrease in PCSK9 degradation which leads to the increase of LDL-C	β* (−0.315); SE (0.037); p**(1.94 x 10^−17)	3290	1268 patients receiving statin therapy and 2022 patients receiving statin-free therapy	Germany	Mendelian randomization study (observational study)	[73]
1:55520994	C>T			β* (−0.085); SE (0.012); p** (4.40x10^−12)
rs45448095	G>A			β* (−0.052); SE (0.009); p** (7.41x10^−09)
rs2479409	G>T			OR (2.3); 95% CI (1.73–3.07); p < 0.0001
rs2781666	C>T	ARG-1	Increase concentration of LDL, triglycerides, and total cholesterol	OR (2.3); 95% CI (1.71–3.16); p < 0.0001	200 families	Families that have CHD in three generations	Pakistan	Case-control study	[36]
rs187238	G>A			OR (2.3); 95% CI (1.71–3.16); p < 0.0001
rs12041331	G>A/C	PEAR1	Affects ADP-induced platelet aggregation	OR (1.4); 95% CI (1.00–2.05); p (0.047)	290	Have a history of ischemia	China	Randomized controlled trial	[59]
rs2644592	T>C	P2Y12		OR (0.5); 95% CI (0.37–0.90); p (0.016)
rs11249454	G>A,C,T	UGT2A1		OR (1.5); 95% CI (1.04–2.20); p (0.029)
rs4244285	A>G	CYP2C19	Reduces the antiplatelet potency	OR (12.2); 95% CI (1.33–112.59); p (0.02)	241	CHD patient	China	Case-control study	[31]
rs2241880	A>C,G	ATG16L1	Increase in intima-media thickness (BMI)	p (0.037)	210	Post-menopausal women	Brazil	Cross-sectional study	[57]
rs1800795	C>A,G,T	IL-6	Immune/inflammatory response and arterial lesions	OR (2.4); 95% CI (1.31–4.72); p (0.003)	447	316 men and 131 women (mean age 61.2 ± 9.4 years) underwent coronary angiography	Russia	Cohort study	[51]
rs2803495	C>T	TREML4	Increased TREML4 mRNA expression in leukocytes	OR (1.7); 95% CI (0.50–5.60); p (0.409)	137	30–74 years old underwent coronary angiography for the diagnosis of CHD	Brazil	Cross-Sectional Study	[45]
rs2803496	C>T			OR (7.3); 95% CI (1.90–27.50); p (0.03)
rs2291521	A>G	CUBN	Increased homocysteine	OR (1.5); 95% CI (1.11–1.97); p (0.008)	452	CHD patients	South Korea	Case–control study	[33]
rs55783344	A>G	HNF1A	Increased LDL	OR (1.5); 95% CI (1.11–2.02); p (0.007)
rs17269397	T>A,C	LIPC	Arteriosclerosis	OR (0.7); 95% CI (0.52–1.01); p (0.062)
rs1801260	C>T	CLOCK	Overexpression of platelets	OR (4.8); 95% CI (2.00–11.35); p (0.000304)	204	CHD patients	China	Cohort Study	[62]
rs3745406	A>G	PRKCG		OR (0.3); 95% CI (0.24–0.63); p (0.000164)
rs10861688	T>G	CRY1		OR (2.8); 95% CI; (1.59–4.91); p (0.000331)
rs2007044	A>G	CACNA1C		OR (2.8); 95%Cl (1.53–5.22); p (0.001)
rs1800872	T>G	IL-10	Immune/inflammatory response	OR (1.8); 95% CI (1.04–3.16); p (0.03)	984	948 people including 307 healthy controls and 641 patients.	Iran	Case-control study	[55]

Notes: *Ratio Estimator. Estimating causal effect in Mendelian randomization study. **Significance value was set to P < 5×10⁻⁸.

Abbreviations: SNPs, single nucleotide polymorphisms; IL, interleukin; MTHFR, methylenetetrahydrofolate; MTR, methyltransferase; CR1, complement receptor 1; LPA, Lipoprotein A; PCSK9, proprotein convertase subtilisin/kexin type 9; ARG-1, Arginase-1; PEAR1, platelet endothelial aggregation receptor 1; P2Y12, P2Y purinoceptor 12; UGT2A1, UDP Glucuronosyltransferase Family 2 Member A1; CRISPLD1, Cysteine Rich Secretory Protein LCCL Domain Containing 1; ATG16L1, Autophagy Related 16 Like 1; TREML4, Triggering Receptor Expressed On Myeloid Cells Like 4; LIPC, Lipase C; CLOCK, Circadian Locomotor Output Cycles Kaput; PRKCG, Protein kinase C gamma; CRY1, Cryptochrome Circadian Regulator 1; CACNA1C, calcium voltage-gated channel subunit alpha1 C; HNF1A, hepatocyte nuclear factor 1 homeobox A; OR, odds ratio; CI, confidence interval; A, adenine; T, thymine; G, guanine; C, cytosine; SE, standard error.

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