Effects of A379V variant of the Lp-PLA 2 gene on Lp-PLA2 activity and markers of oxidative stress and endothelial function in Koreans

Jey Sook Chae, Jung Hyun Kwak, Minjoo Kim, Kyoung Hun Shin, Sang Hyun Lee, Tae Sook Jeong, Jong Ho Lee

Research output: Contribution to journalArticle

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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-PGF 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-PGF, 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.

Original languageEnglish
Pages (from-to)477-484
Number of pages8
JournalJournal of Thrombosis and Thrombolysis
Volume38
Issue number4
DOIs
Publication statusPublished - 2014 Oct 2

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1-Alkyl-2-acetylglycerophosphocholine Esterase
Oxidative Stress
Genotype
Genes
Selectins
Dinoprost
Single Nucleotide Polymorphism
Platelet Activating Factor
Creatinine
Cardiovascular Diseases
Alleles

All Science Journal Classification (ASJC) codes

  • Hematology
  • Cardiology and Cardiovascular Medicine

Cite this

Chae, Jey Sook ; Kwak, Jung Hyun ; Kim, Minjoo ; Shin, Kyoung Hun ; Lee, Sang Hyun ; Jeong, Tae Sook ; Lee, Jong Ho. / Effects of A379V variant of the Lp-PLA 2 gene on Lp-PLA2 activity and markers of oxidative stress and endothelial function in Koreans. In: Journal of Thrombosis and Thrombolysis. 2014 ; Vol. 38, No. 4. pp. 477-484.
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title = "Effects of A379V variant of the Lp-PLA 2 gene on Lp-PLA2 activity and markers of oxidative stress and endothelial function in Koreans",
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.",
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Effects of A379V variant of the Lp-PLA 2 gene on Lp-PLA2 activity and markers of oxidative stress and endothelial function in Koreans. / Chae, Jey Sook; Kwak, Jung Hyun; Kim, Minjoo; Shin, Kyoung Hun; Lee, Sang Hyun; Jeong, Tae Sook; Lee, Jong Ho.

In: Journal of Thrombosis and Thrombolysis, Vol. 38, No. 4, 02.10.2014, p. 477-484.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Effects of A379V variant of the Lp-PLA 2 gene on Lp-PLA2 activity and markers of oxidative stress and endothelial function in Koreans

AU - Chae, Jey Sook

AU - Kwak, Jung Hyun

AU - Kim, Minjoo

AU - Shin, Kyoung Hun

AU - Lee, Sang Hyun

AU - Jeong, Tae Sook

AU - Lee, Jong Ho

PY - 2014/10/2

Y1 - 2014/10/2

N2 - 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.

AB - 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.

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