Carriage of the V279F homozygous genotype, a rare allele, within the gene encoding Lp-PLA2 leads to changes in circulating intermediate metabolites in individuals without metabolic syndrome

Aim: Identifying differences in plasma metabolic profiling between Lp-PLA2 279VV and 279FF in individuals without metabolic syndrome (MetS) can be used to elucidate the roles of novel Lp-PLA2 activities in normal physiological processes.Methods: Non-MetS individuals with 279FF (n=36) and age-, sex- and BMI-matched VV subjects (n=36) were included in this analysis.Results: The FF subjects exhibited no appreciable enzyme activity. No significant differences were observed between the VV and FF subjects in the serum lipid profiles or hs-CRP, plasma ox-LDL, MDA or urinary 8-epi-PGF2α levels. The FF subjects also showed lower activities of lyso-phosphatidylcholine (lysoPC) (16:0) (p=0.003) and oleamide (p＜0.001) and a higher activity of L-tryptophan (p=0.016) than the VV subjects. In addition, the Lp-PLA2 activity positively correlated with the lysoPC (16:0) and lysoPC (18:0) activities and negatively correlated with the PC (16:0/22:6) and L-tryptophan activities in the VV subjects. Furthermore, in the VV subjects, the lysoPC (16:0) and lysoPC (18:0) activities negatively correlated with the presence of PCs containing 14:0/20:2, 14:0/22:4 and 16:0/22:6, while the oleamide activity exhibited a strong positive correlation with lysoPCs and a negative correlation with PCs, whereas the relationship between oleamide and lysoPCs and PCs was weaker in the FF subjects.Conclusions: The present results indicate that the natural absence of the plasma Lp-PLA2 activity due to carriage of the Lp-PLA2 279FF genotype may reduce the generation of lysoPC (16:0) and oleamide and thereby enhance the activity of plasma tryptophan in normal physiological processes.