Effects of A379V variant of the Lp-PLA sub(2) gene on Lp-PLA sub(2) activity and markers of oxidative stress and endothelial function in Koreans

• Published in: Journal of thrombosis and thrombolysis Vol. 38; no. 4; pp. 477 - 484
• Main Authors: Chae, Jey Sook, Kwak, Jung Hyun, Kim, Minjoo, Shin, Kyoung Hun, Lee, Sang-Hyun, Jeong, Tae-Sook, Lee, Jong Ho
• Format: Journal Article
• Language: English
• Published: 01.11.2014
• ISSN: 0929-5305; 1573-742X
• DOI: 10.1007/s11239-014-1074-5

A379V variant in the lipoprotein-associated phospholipase A sub(2) (Lp-PLA sub(2)) gene is known to be functional, but there are contradicting data concerning the A379V polymorphism, Lp-PLA sub(2) activity and cardiovascular disease risk. We determined the interplay between A379V SNP, Lp-PLA sub(2) 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-PLA sub(2) polymorphism (A379V and V279F). Lp-PLA sub(2) activity and markers of oxidative stress and endothelial function were measured. Lp-PLA sub(2) 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-PGF sub(2 alpha ) 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 plus or minus 14, A/V; 1,371 plus or minus 26, V/V; 1,199 plus or minus 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-PLA sub(2) activities in the 279 V/V group. However, the associations of the A379V SNP with levels of 8-epi-PGF sub(2 alpha ), 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-PLA sub(2) for platelet-activating factor substrate, towards a more anti-oxidative or anti-atherogenic form.