The V279F polymorphism might change protein character and immunogenicity in Lp-PLA2 protein

Abstract

Background: Lipoprotein-associated phospholipase A2 (Lp-PLA2) plays a strong role in the occurrence of certain cardiovascular disease processes. Polymorphisms at the protein level are also estimated to correlate with increased risk factors for heart attacks. One such polymorphism is the V279F polymorphism in Lp-PLA2 which results in a change in enzyme performance capability. This in turn implies a reduced risk of acute myocardial infarct (AMI) in Korean and Indonesian subpopulations.

Aim: This study aimed to analyze changes in protein properties, structure, energy stability, epitope, and immunogenicity that are due to the substitution of the Valine (V) amino acid at position 279 to Phenylalanine (F) in the Lp-PLA2 protein.

Methodology: The role of Lp-PLA2 in the cardiovascular process and in AMI was analyzed based on the protein-protein network according to the BioGRID, MENTHA, and STRING databases. Protein properties and energy stability were examined by FoldX; this was followed by identification of epitope using ElliPro. The immunogenicity was evaluated in vivo by injecting the protein into mice and subsequently measuring their antibody production using the ELISA technique.

Results: The substitution of Valine for Phenylalanine was predicted to increase protein stability and epitope shifts. Further studies on animal experiments exhibit that the 279V variant is able to induce IgG production better than the 279F variant.

Conclusion: Based on these data, it can be concluded that the V279F polymorphism influences the surface structure, energy stability, epitope and immunogenicity of the Lp-PLA2 protein. The changes in the immunogenicity and epitope shift indicated that the protein is valuable as a biomarker for use in acute myocardial infarct. The results of this study provide an opportunity to develop monoclonal antibodies that are specifically able to identify V279F polymorphisms as a predictor of the risk of acute myocardial infarct.

Keywords: Epitope shifting, Cardiovascular, PAF-AH, Phospholipase A2, PLA2G7