Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Mar 6;26(5):2337.
doi: 10.3390/ijms26052337.

The Impact of SNP Score on Low-Density Lipoprotein Cholesterol Concentration and Coronary Artery Disease

Darius Čereškevičius  1 , Ieva Čiapienė  1 , Ali Aldujeli  1 , Vytautas Zabiela  1 , Vaiva Lesauskaitė  1 , Kristina Zubielienė  1 , Vytautas Raškevičius  1 , Diana Žaliaduonytė  2 , Ramūnas Unikas  3 , Robertas Pranevičius  1 , Ignas Simanauskas  1 , Giedrė Bakšytė  3 , Abdonas Tamošiūnas  1 , Dalia Lukšienė  1 , Gintarė Šakalytė  1 , Vacis Tatarūnas  1
Affiliations

The Impact of SNP Score on Low-Density Lipoprotein Cholesterol Concentration and Coronary Artery Disease

Darius Čereškevičius et al. Int J Mol Sci. .

Abstract

Hypercholesterolemia, characterized by elevated levels of low-density lipoprotein cholesterol (LDL-C), along with inflammation, is a well-known risk factor for developing atherosclerosis and coronary artery disease (CAD). Many patients with hypercholesterolemia may carry inherited genetic variants that are not part of the commonly recognized mutations in the LDLR, APOB, LDLRAP1, and PCSK9 genes. These genetic variants may have cumulative effects that contribute to increased LDL-C levels and CAD development. The polygenic risk score (PRS) may provide an essential tool for evaluating an individual's genetic predisposition to these conditions. This pilot study aimed to investigate the impact of the PRS calculated from specific single nucleotide polymorphisms (SNPs) associated with LDL cholesterol (LDL-C)-namely, CELSR2 rs629301, APOB rs1367117, ABCG8 rs6544713, LDLR rs6511720, APOE rs429358, and rs7412-on LDL-C levels in both healthy individuals with elevated LDL-C levels (>2.6 mmol/L) and those diagnosed with ST-segment elevation myocardial infarction (STEMI). A total of 61 healthy individuals with high LDL-C levels (>2.6 mmol/L) and 93 STEMI patients were selected for the study. The High-Resolution Melting Polymerase Chain Reaction (HRM PCR) method was adopted and sequencing techniques were employed to identify the specific single nucleotide polymorphisms (SNPs) of interest. The patient group exhibited a PRS of 0.824 (with a range of -0.62 to 1.174) compared to 0.674 (range: -0.176 to 0.974) in healthy individuals, indicating a higher genetic predisposition to elevated LDL-C levels (p = 0.001) in patients. Interestingly, patients had lower LDL-C concentrations than healthy individuals. Additionally, a more significant number of patients were past smokers and statin users. The PRS calculations revealed that patients with a higher PRS had increased odds of experiencing an MI, with an odds ratio of 12.044 (95% confidence interval: 1.551-93.517, p = 0.017). Similarly, smokers showed even higher odds, with an odds ratio of 24.962 (95% CI: 7.171-86.890, p < 0.001). Among healthy individuals, those with a higher PRS had increased odds of having an LDL-C concentration greater than 4.9 mmol/L (odds ratio: 20.391, 95% CI: 1.116-358.486, p = 0.039). However, no significant association was found between the PRS and LDL-C levels in the patient group during hospitalization (p = 0.782). This pilot study shows that PRS can be employed to evaluate the risk of MI and to estimate concentrations greater than 4.9 mmol/L LDL-C in healthy individuals.

Keywords: PRS; SNP score; coronary artery disease; hypercholesterolemia; low-density lipoprotein cholesterol.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
PRS distribution in patient and comparison groups representing counts of individuals.
Figure 2
Figure 2
Patient and healthy population sample and analysis methods.
See this image and copyright information in PMC

References

    1. Mensah G.A., Roth G.A., Fuster V. The Global Burden of Cardiovascular Diseases and Risk Factors: 2020 and Beyond. J. Am. Coll. Cardiol. 2019;74:2529–2532. doi: 10.1016/j.jacc.2019.10.009. - DOI - PubMed
    1. Khan M.A., Hashim M.J., Mustafa H., Baniyas M.Y., Al Suwaidi S.K.B.M., AlKatheeri R., Alblooshi F.M.K., Almatrooshi M.E.A.H., Alzaabi M.E.H., Al Darmaki R.S., et al. Global Epidemiology of Ischemic Heart Disease: Results from the Global Burden of Disease Study. Cureus. 2020;12:e9349. doi: 10.7759/cureus.9349. - DOI - PMC - PubMed
    1. Ridker P.M., Moorthy M.V., Cook N.R., Rifai N., Lee I.M., Buring J.E. Inflammation, Cholesterol, Lipoprotein(a), and 30-Year Cardiovascular Outcomes in Women. N. Engl. J. Med. 2024;391:2087–2097. doi: 10.1056/NEJMoa2405182. - DOI - PMC - PubMed
    1. Linton M.F., Yancey P.G., Davies S.S., Jerome W.G., Linton E.F., Song W.L., Doran A.C., Vickers K.C. In: The Role of Lipids and Lipoproteins in Atherosclerosis. Feingold K.R., Anawalt B., Blackman M.R., Boyce A., Chrousos G., Corpas E., editors. MDText.Com, Inc.; South Dartmouth, MA, USA: 2019.
    1. Nordestgaard B.G., Varbo A. Triglycerides and Cardiovascular Disease. Lancet. 2014;384:626–635. doi: 10.1016/S0140-6736(14)61177-6. - DOI - PubMed

Substances

LinkOut - more resources