A379V variant in the lipoprotein-associated phospholipase A2 (Lp-PLA2) gene is known to be functional, but there are contradicting data concerning the A379V polymorphism, Lp-PLA2 activity and cardiovascular disease risk. We determined the interplay between A379V SNP, Lp-PLA2 activity, and markers of oxidative stress and endothelial function with and without the effect of V279F variant. 3,220 unrelated and healthy Koreans (40–79 years) were genotyped for the Lp-PLA2 polymorphism (A379V and V279F). Lp-PLA2 activity and markers of oxidative stress and endothelial function were measured. Lp-PLA2 activity was 3.9 % higher in A/V subjects (n = 821) and 7.8 % in V/V (n = 79) than in those with A/A (n = 2,320). Urinary levels of 8-epi-PGF2α were significantly lower in subjects with the A/V or the V/V genotype than in those with the A/A genotype (A/A; 1,426 ± 14, A/V; 1,371 ± 26, V/V; 1,199 ± 58 pg/mg creatinine, P = 0.003). Subjects with the 379 V/V genotype had lower serum concentrations of sICAM-1 and p-selectin compared to those with the A/A or the A/V genotype. When subjects were further stratified into subgroups based on the combination of A379V and V279F genotypes, there was no significant association between A379V genotypes and Lp-PLA2 activities in the 279 V/V group. However, the associations of the A379V SNP with levels of 8-epi-PGF2α, sICAM-1, and p-selectin remained in the subset analysis based on the V279F genotypes. This study showed a reduction in oxidative stress in subjects carrying 379V allele and the recessive effect of the A379V on the endothelial function. It is likely that the A379V polymorphism has a qualitative effect, probably by disrupting the affinity of Lp-PLA2 for platelet-activating factor substrate, towards a more anti-oxidative or anti-atherogenic form.
Bibliographical noteFunding Information:
Acknowledgments The authors thank the research volunteers who participated in the studies described in this article. This research was supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2006-2005306, 2010-0015017, and 2012M3A9C4048762).
All Science Journal Classification (ASJC) codes
- Cardiology and Cardiovascular Medicine