Effects of A379V variant of the Lp-PLA2 gene on Lp-PLA2 activity and markers of oxidative stress and endothelial function in Koreans

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Title
Effects of A379V variant of the Lp-PLA2 gene on Lp-PLA2 activity and markers of oxidative stress and endothelial function in Koreans
Author(s)
J S Chae; J H Kwak; M Kim; K H Shin; S H Lee; Tae Sook Jeong; J H Lee
Bibliographic Citation
Journal of Thrombosis and Thrombolysis, vol. 38, no. 4, pp. 477-484
Publication Year
2014
Abstract
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.
Keyword
A379VLipoprotein-associated phospholipase A2p-SelectinSoluble intercellular adhesion molecule-1Urinary 8-epi-PGF2α
ISSN
0929-5305
Publisher
Springer
DOI
http://dx.doi.org/10.1007/s11239-014-1074-5
Type
Article
Appears in Collections:
Division of Biomaterials Research > Industrial Bio-materials Research Center > 1. Journal Articles
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