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
ABSTRACT
Background: Angiotensin I-converting enzyme [ACE] has two homologous catalytic domains, the N- and C-domains. Our previous study suggested that Alu insertion [I allele] in the intron 16 of ACE resulted in premature codon termination. The I allele has only one active site in the N-domain while the Alu deletion [D allele] still has two active sites of ACE. Therefore the effect of I/ D polymorphism of ACE on the enzyme's ability to catalyse bradykinin is still not widely known
Aims: This study aimed to examine the serum bradykinin level in hypertensive patients with I/D polymorphism of ACE, who were treated with ACE inhibitor
Subjects and methods: The serum bradykinin and I/D polymorphism have been detected in 64 hypertensive patients taking ACE inhibitor [lisinopril or captopril] for at least eight weeks with good medication adherence. The binding affinity of ACE with its receptor was calculated by molecular docking
Results: The findings show that genotype II is more frequent in the population the researchers observed [53.12%] compared to ID [23.44%] and DD [23.44%] variances. On the other hand, the bradykinin level is not affected by genotype of the ACE genes on the population. Bradykinin increases in patients with genotype II who are given captopril, but decreases in patients treated with lisinopril. Nevertheless, there is no statistically significant difference
Conclusion: This study suggests that the polymorphism might not significantly affect the serum bra-dykinin level in hypertensive patients taking ACE inhibitors