title: Effects of A379V variant of the Lp-PLA 2 gene on Lp-PLA 2 activity and markers of oxidative stress and endothelial function in Koreans.
abstract: A379V variant in the lipoprotein-associated phospholipase A2 (Lp-PLA 2) 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-PLA 2 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.
authors.affiliation: Yonsei University Research Institute of Science for Aging, Yonsei University, Seoul, Korea.
authors.forename: Jey Sook
authors.initials: JS
authors.lastname: Chae
authors.forename: Jung Hyun
authors.initials: JH
authors.lastname: Kwak
authors.forename: Minjoo
authors.initials: M
authors.lastname: Kim
authors.forename: Kyoung Hun
authors.initials: KH
authors.lastname: Shin
authors.forename: Sang-Hyun
authors.initials: SH
authors.lastname: Lee
authors.forename: Tae-Sook
authors.initials: TS
authors.lastname: Jeong
authors.forename: Jong Ho
authors.initials: JH
authors.lastname: Lee
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood / Q000235:genetics*; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D004730:Endothelium, Vascular / Q000502:physiology*; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D005819:Genetic Markers / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: D005819:Genetic Markers; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C526684:PLA2G7 protein, human