Effects of V279F in the Lp-PLA2 gene on markers of oxidative stress and inflammation in Koreans

Jean Kyung Paik, Jey Sook Chae, Yangsoo Jang, Ji Young Kim, Oh Yoen Kim, Tae Sook Jeong, Sang Hyun Lee, Jong Ho Lee

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Abstract

Background: A single nucleotide polymorphism (SNP), V279F, in the lipoprotein-associated phospholipase A2 (Lp-PLA2) gene is known to influence enzyme activity. It is unclear whether Lp-PLA2 exerts pro- or antiatherogenic effects in humans. We investigated the interplay between V279F, Lp-PLA2 activity, oxidative stress and inflammation. Methods: We genotyped 2914 healthy Koreans (43-79years) for the Lp-PLA2 V279F and measured anthropometric parameters, lipid profile, fatty acid composition, lipid peroxides, inflammatory markers and Lp-PLA2 levels. Results: Lp-PLA2 activity was 24% lower in V/F subjects (n=641) than in those with the V/V genotype (n=2227). Enzyme activity was undetectable in F/F subjects. Lp-PLA2 activity was positively correlated with LDL-cholesterol (r=0.134, P<0.001), ox-LDL (r=0.064, P<0.01), 8-epi-PGF (r=0.198, P<0.001), free fatty acid (r=0.082, P<0.001), and fibrinogen (r=0.112, P<0.01) levels. Additionally, ox-LDL, 8-epi-PGF, free fatty acid, and fibrinogen levels were positively correlated with hs-CRP. V279F was associated with LDL-cholesterol and arachidonic acid (AA) in serum phospholipid. F/F subjects had lower LDL-cholesterol than V/V subjects (V/V: 120.9±0.69, V/F: 119.4±1.26, F/F: 109.2±4.84mg/dl, P=0.025). A significant association between the F/F genotype and increasing AA in serum phospholipids was found in subjects with high LDL-cholesterol (≥130mg/dl) (P=0.003) but not in those with low LDL-cholesterol (<130mg/dl). F/F subjects in the high LDL-cholesterol group had CRP concentrations about three times higher than those with V/V or V/F genotypes (V/V: 1.25±0.09, V/F: 0.97±0.12, F/F: 3.20±0.88mg/dl, P<0.001). Conclusions: The recessive effects of Lp-PLA2 V279F on LDL-cholesterol and significant correlations between Lp-PLA2 activity and LDL-cholesterol, 8-epi-PGF and fibrinogen support a pro-oxidative or pro-atherogenic role for this enzyme. Paradoxically, the combination of the complete deficiency of Lp-PLA2 activity and high LDL-cholesterol enhanced lipid peroxidation and inflammation.

Original languageEnglish
Pages (from-to)486-493
Number of pages8
JournalClinica Chimica Acta
Volume411
Issue number7-8
DOIs
Publication statusPublished - 2010 Apr 1

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1-Alkyl-2-acetylglycerophosphocholine Esterase
Oxidative stress
LDL Cholesterol
Oxidative Stress
Genes
Inflammation
Dinoprost
Fibrinogen
Genotype
Enzyme activity
Nonesterified Fatty Acids
Arachidonic Acid
Phospholipids
Enzymes
Lipids
Lipid Peroxides
Polymorphism
Serum
Lipid Peroxidation
Single Nucleotide Polymorphism

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Paik, Jean Kyung ; Chae, Jey Sook ; Jang, Yangsoo ; Kim, Ji Young ; Kim, Oh Yoen ; Jeong, Tae Sook ; Lee, Sang Hyun ; Lee, Jong Ho. / Effects of V279F in the Lp-PLA2 gene on markers of oxidative stress and inflammation in Koreans. In: Clinica Chimica Acta. 2010 ; Vol. 411, No. 7-8. pp. 486-493.
@article{754e884aa1c64687890bd1a1d5daee64,
title = "Effects of V279F in the Lp-PLA2 gene on markers of oxidative stress and inflammation in Koreans",
abstract = "Background: A single nucleotide polymorphism (SNP), V279F, in the lipoprotein-associated phospholipase A2 (Lp-PLA2) gene is known to influence enzyme activity. It is unclear whether Lp-PLA2 exerts pro- or antiatherogenic effects in humans. We investigated the interplay between V279F, Lp-PLA2 activity, oxidative stress and inflammation. Methods: We genotyped 2914 healthy Koreans (43-79years) for the Lp-PLA2 V279F and measured anthropometric parameters, lipid profile, fatty acid composition, lipid peroxides, inflammatory markers and Lp-PLA2 levels. Results: Lp-PLA2 activity was 24{\%} lower in V/F subjects (n=641) than in those with the V/V genotype (n=2227). Enzyme activity was undetectable in F/F subjects. Lp-PLA2 activity was positively correlated with LDL-cholesterol (r=0.134, P<0.001), ox-LDL (r=0.064, P<0.01), 8-epi-PGF2α (r=0.198, P<0.001), free fatty acid (r=0.082, P<0.001), and fibrinogen (r=0.112, P<0.01) levels. Additionally, ox-LDL, 8-epi-PGF2α, free fatty acid, and fibrinogen levels were positively correlated with hs-CRP. V279F was associated with LDL-cholesterol and arachidonic acid (AA) in serum phospholipid. F/F subjects had lower LDL-cholesterol than V/V subjects (V/V: 120.9±0.69, V/F: 119.4±1.26, F/F: 109.2±4.84mg/dl, P=0.025). A significant association between the F/F genotype and increasing AA in serum phospholipids was found in subjects with high LDL-cholesterol (≥130mg/dl) (P=0.003) but not in those with low LDL-cholesterol (<130mg/dl). F/F subjects in the high LDL-cholesterol group had CRP concentrations about three times higher than those with V/V or V/F genotypes (V/V: 1.25±0.09, V/F: 0.97±0.12, F/F: 3.20±0.88mg/dl, P<0.001). Conclusions: The recessive effects of Lp-PLA2 V279F on LDL-cholesterol and significant correlations between Lp-PLA2 activity and LDL-cholesterol, 8-epi-PGF2α and fibrinogen support a pro-oxidative or pro-atherogenic role for this enzyme. Paradoxically, the combination of the complete deficiency of Lp-PLA2 activity and high LDL-cholesterol enhanced lipid peroxidation and inflammation.",
author = "Paik, {Jean Kyung} and Chae, {Jey Sook} and Yangsoo Jang and Kim, {Ji Young} and Kim, {Oh Yoen} and Jeong, {Tae Sook} and Lee, {Sang Hyun} and Lee, {Jong Ho}",
year = "2010",
month = "4",
day = "1",
doi = "10.1016/j.cca.2009.12.021",
language = "English",
volume = "411",
pages = "486--493",
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Effects of V279F in the Lp-PLA2 gene on markers of oxidative stress and inflammation in Koreans. / Paik, Jean Kyung; Chae, Jey Sook; Jang, Yangsoo; Kim, Ji Young; Kim, Oh Yoen; Jeong, Tae Sook; Lee, Sang Hyun; Lee, Jong Ho.

In: Clinica Chimica Acta, Vol. 411, No. 7-8, 01.04.2010, p. 486-493.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Effects of V279F in the Lp-PLA2 gene on markers of oxidative stress and inflammation in Koreans

AU - Paik, Jean Kyung

AU - Chae, Jey Sook

AU - Jang, Yangsoo

AU - Kim, Ji Young

AU - Kim, Oh Yoen

AU - Jeong, Tae Sook

AU - Lee, Sang Hyun

AU - Lee, Jong Ho

PY - 2010/4/1

Y1 - 2010/4/1

N2 - Background: A single nucleotide polymorphism (SNP), V279F, in the lipoprotein-associated phospholipase A2 (Lp-PLA2) gene is known to influence enzyme activity. It is unclear whether Lp-PLA2 exerts pro- or antiatherogenic effects in humans. We investigated the interplay between V279F, Lp-PLA2 activity, oxidative stress and inflammation. Methods: We genotyped 2914 healthy Koreans (43-79years) for the Lp-PLA2 V279F and measured anthropometric parameters, lipid profile, fatty acid composition, lipid peroxides, inflammatory markers and Lp-PLA2 levels. Results: Lp-PLA2 activity was 24% lower in V/F subjects (n=641) than in those with the V/V genotype (n=2227). Enzyme activity was undetectable in F/F subjects. Lp-PLA2 activity was positively correlated with LDL-cholesterol (r=0.134, P<0.001), ox-LDL (r=0.064, P<0.01), 8-epi-PGF2α (r=0.198, P<0.001), free fatty acid (r=0.082, P<0.001), and fibrinogen (r=0.112, P<0.01) levels. Additionally, ox-LDL, 8-epi-PGF2α, free fatty acid, and fibrinogen levels were positively correlated with hs-CRP. V279F was associated with LDL-cholesterol and arachidonic acid (AA) in serum phospholipid. F/F subjects had lower LDL-cholesterol than V/V subjects (V/V: 120.9±0.69, V/F: 119.4±1.26, F/F: 109.2±4.84mg/dl, P=0.025). A significant association between the F/F genotype and increasing AA in serum phospholipids was found in subjects with high LDL-cholesterol (≥130mg/dl) (P=0.003) but not in those with low LDL-cholesterol (<130mg/dl). F/F subjects in the high LDL-cholesterol group had CRP concentrations about three times higher than those with V/V or V/F genotypes (V/V: 1.25±0.09, V/F: 0.97±0.12, F/F: 3.20±0.88mg/dl, P<0.001). Conclusions: The recessive effects of Lp-PLA2 V279F on LDL-cholesterol and significant correlations between Lp-PLA2 activity and LDL-cholesterol, 8-epi-PGF2α and fibrinogen support a pro-oxidative or pro-atherogenic role for this enzyme. Paradoxically, the combination of the complete deficiency of Lp-PLA2 activity and high LDL-cholesterol enhanced lipid peroxidation and inflammation.

AB - Background: A single nucleotide polymorphism (SNP), V279F, in the lipoprotein-associated phospholipase A2 (Lp-PLA2) gene is known to influence enzyme activity. It is unclear whether Lp-PLA2 exerts pro- or antiatherogenic effects in humans. We investigated the interplay between V279F, Lp-PLA2 activity, oxidative stress and inflammation. Methods: We genotyped 2914 healthy Koreans (43-79years) for the Lp-PLA2 V279F and measured anthropometric parameters, lipid profile, fatty acid composition, lipid peroxides, inflammatory markers and Lp-PLA2 levels. Results: Lp-PLA2 activity was 24% lower in V/F subjects (n=641) than in those with the V/V genotype (n=2227). Enzyme activity was undetectable in F/F subjects. Lp-PLA2 activity was positively correlated with LDL-cholesterol (r=0.134, P<0.001), ox-LDL (r=0.064, P<0.01), 8-epi-PGF2α (r=0.198, P<0.001), free fatty acid (r=0.082, P<0.001), and fibrinogen (r=0.112, P<0.01) levels. Additionally, ox-LDL, 8-epi-PGF2α, free fatty acid, and fibrinogen levels were positively correlated with hs-CRP. V279F was associated with LDL-cholesterol and arachidonic acid (AA) in serum phospholipid. F/F subjects had lower LDL-cholesterol than V/V subjects (V/V: 120.9±0.69, V/F: 119.4±1.26, F/F: 109.2±4.84mg/dl, P=0.025). A significant association between the F/F genotype and increasing AA in serum phospholipids was found in subjects with high LDL-cholesterol (≥130mg/dl) (P=0.003) but not in those with low LDL-cholesterol (<130mg/dl). F/F subjects in the high LDL-cholesterol group had CRP concentrations about three times higher than those with V/V or V/F genotypes (V/V: 1.25±0.09, V/F: 0.97±0.12, F/F: 3.20±0.88mg/dl, P<0.001). Conclusions: The recessive effects of Lp-PLA2 V279F on LDL-cholesterol and significant correlations between Lp-PLA2 activity and LDL-cholesterol, 8-epi-PGF2α and fibrinogen support a pro-oxidative or pro-atherogenic role for this enzyme. Paradoxically, the combination of the complete deficiency of Lp-PLA2 activity and high LDL-cholesterol enhanced lipid peroxidation and inflammation.

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