Unveiling the Synergy of Serum Lipoprotein-Associated Phospholipase A2 and PLA2G7 Gene Polymorphism (rs1805017) as Key Determinants of Coronary Artery Disease Risk and Severity: Implications for Early Intervention

Background Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a key enzyme selectively expressed in unstable, rupture-prone atherosclerotic plaques. Previous research has established a strong link between the PLA2G7 gene and the development of coronary artery disease (CAD). While traditional risk factors like cholesterol levels and blood pressure are valuable, there remains a need for more specific biomarkers to identify individuals at heightened risk of atherosclerosis before the onset of clinical symptoms. Our study aimed to investigate the association between serum Lp-PLA2 levels, lipid parameters, cardiac markers, and the rs1805017 variant within the PLA2G7 gene. By exploring these factors, we sought to enhance the assessment of CAD risk and severity. Materials and methods It is a Cross-sectional, case-control study, that recruited 125 subjects, comprising 75 angiographically proven CAD cases and 50 age-sex and ethnically matched controls of a South Indian population. Serum biomarkers were processed according to standard commercial kits. A group of 100 subjects underwent genotyping using Sanger's sequencing method. Results Out of the total study population, 25% of the patients were young men (<45 years). We quantitatively estimated the serum Lp-PLA2 levels and evaluated any possible association of serum Lp-PLA2 levels with all the genotypes of R92H (rs1805017) located on Exon 4 of the PLA2G7 gene on chromosome 6. In CAD patients, we found a significant positive correlation of the lipid profile, Lp(a), hs Troponin I, and Lp-PLA2, but a negative correlation with high-density lipoprotein cholesterol (HDL-C) levels. The genotype frequency distributions of the R92H (rs1805017) polymorphisms were GG (17.9%), GA (35.7%), and AA (46.4%) in the control group, and GG (20.3%), GA (30.4%), and AA (49.3%) in CAD cases. The prevalence of the homozygous genotype and serum Lp-PLA2 levels was highest in patients with triple vessel disease (TVD). After correction, logistic regression showed homozygosity as the main independent risk predictor of CAD (p=0.0087). Receiver operating characteristic (ROC) curves revealed that among all biomarkers tested, Lp-PLA2 showed a higher area under the curve (AUC: 0.935), indicating excellent diagnostic ability with a cutoff >392 ng/ml and a sensitivity of 88.2% and specificity of 90.9% in predicting the risk and severity of CAD. Conclusions Elevated serum Lp-PLA2 levels and homozygosity of rs1805017 were significantly associated with the risk and severity of disease (TVD). Single nucleotide polymorphism (SNP) analysis can be used as a risk stratification test. Alternatively, as elevated Lp-PLA2 is an indicator of unstable rupture-prone plaques, it can be used as an economical, noninvasive risk and severity predictor, especially in places where coronary angiography (CAG) is not available. Although further research is warranted, these findings can assist in primordial prevention or prescribing a prompt therapeutic algorithm to decrease disease mortality.