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.