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

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 <i>LDLR</i>, <i>APOB</i>, <i>LDLRAP1</i>, and <i>PCSK9</i> 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, <i>CELSR2 rs629301</i>, <i>APOB rs1367117</i>, <i>ABCG8 rs6544713</i>, <i>LDLR rs6511720</i>, <i>APOE rs429358</i>, and <i>rs7412</i>-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 (<i>p</i> = 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, <i>p</i> = 0.017). Similarly, smokers showed even higher odds, with an odds ratio of 24.962 (95% CI: 7.171-86.890, <i>p</i> < 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, <i>p</i> = 0.039). However, no significant association was found between the PRS and LDL-C levels in the patient group during hospitalization (<i>p</i> = 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.