Gender-specific variations in lipoprotein-associated phospholipase A₂ (rs1051931) polymorphism and cardiovascular disease susceptibility in an Egyptian cohort

Abstract Background Lipoprotein-associated phospholipase A₂ (Lp-PLA₂) is a vascular-specific enzyme that hydrolyzes oxidized phospholipids on low-density lipoprotein (LDL-C), thereby promoting vascular inflammation and atherosclerosis. Sex-related differences in lipid metabolism and genetic polymorphisms may influence cardiovascular disease (CVD) risk. This study aimed to evaluate sex-specific variations in lipid profiles, cardiac biomarkers, Lp-PLA₂ activity, and the Ala379Val (rs1051931, G/A) polymorphism in healthy Egyptian adults. Methods One hundred healthy individuals (50 males and 50 females) were recruited. Serum concentrations of triglycerides, total cholesterol (T-C), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total creatine kinase (T-CK), and creatine kinase-MB (CK-MB) were measured. Lp-PLA₂ activity was determined using a colorimetric assay, and genotyping of rs1051931 was performed via PCR-RFLP. Results Males exhibited significantly higher levels of triglycerides, low-density lipoprotein cholesterol (LDL-C), total creatine kinase (T-CK), and creatine kinase-MB (CK-MB), along with lower high-density lipoprotein cholesterol (HDL-C) levels compared to females ( P < 0.05). After adjusting for body mass index (BMI), Lp-PLA₂ activity was elevated in males across all genotypes, with the highest activity observed in individuals carrying the AA genotype. The A allele was more prevalent in males (31%) than in females (25%) ( P < 0.05). Conclusion Sex-specific disparities favoring males in lipid metabolism, cardiac enzyme activity, and the Lp-PLA₂ (G/A) variation may augment their heightened cardiovascular risk. Specifically, Egyptian males possessing the A allele of rs1051931 seem to exhibit increased vulnerability to lipid-induced cardiovascular problems, presumably due to elevated Lp-PLA₂ activity. These findings underscore the need to incorporate sex and genetic profiling into cardiovascular disease risk evaluation and preventive measures, enabling more precise and individualized therapies. Graphical abstract