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

doi:10.1016/j.cca.2009.12.021

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

Research output: Contribution to journal › Article › peer-review

15 Citations (Scopus)

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_2α (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_2α, 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_2α 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 language	English
Pages (from-to)	486-493
Number of pages	8
Journal	Clinica Chimica Acta
Volume	411
Issue number	7-8
DOIs	https://doi.org/10.1016/j.cca.2009.12.021
Publication status	Published - 2010 Apr

Bibliographical note

Funding Information:
This work was funded by 1) National Research Laboratory grant # R0A-2005-000-10144-0 , Ministry of Science and Technology , Seoul, Korea, 2) Korea Health 21 R&D Projects, Ministry of Health & Welfare ( A000385 ), Seoul, Korea, 3) Korea Science and Engineering Foundation (KOSEF) grant ( 2009-0078457 ) , Ministry of Science and Technology , Seoul, Korea, 4) Korea Science and Engineering Foundation (KOSEF) grant ( M10642120002-06 N4212-00210 ) , Ministry of Science and Technology , Seoul, Korea.

All Science Journal Classification (ASJC) codes

Biochemistry
Clinical Biochemistry
Biochemistry, medical

Access to Document

10.1016/j.cca.2009.12.021

Cite this

@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}",

note = "Funding Information: This work was funded by 1) National Research Laboratory grant # R0A-2005-000-10144-0 , Ministry of Science and Technology , Seoul, Korea, 2) Korea Health 21 R&D Projects, Ministry of Health & Welfare ( A000385 ), Seoul, Korea, 3) Korea Science and Engineering Foundation (KOSEF) grant ( 2009-0078457 ) , Ministry of Science and Technology , Seoul, Korea, 4) Korea Science and Engineering Foundation (KOSEF) grant ( M10642120002-06 N4212-00210 ) , Ministry of Science and Technology , Seoul, Korea.",

year = "2010",

month = apr,

doi = "10.1016/j.cca.2009.12.021",

language = "English",

volume = "411",

pages = "486--493",

journal = "Clinica Chimica Acta",

issn = "0009-8981",

publisher = "Elsevier",

number = "7-8",

}

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

N1 - Funding Information: This work was funded by 1) National Research Laboratory grant # R0A-2005-000-10144-0 , Ministry of Science and Technology , Seoul, Korea, 2) Korea Health 21 R&D Projects, Ministry of Health & Welfare ( A000385 ), Seoul, Korea, 3) Korea Science and Engineering Foundation (KOSEF) grant ( 2009-0078457 ) , Ministry of Science and Technology , Seoul, Korea, 4) Korea Science and Engineering Foundation (KOSEF) grant ( M10642120002-06 N4212-00210 ) , Ministry of Science and Technology , Seoul, Korea.

PY - 2010/4

Y1 - 2010/4

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.

UR - http://www.scopus.com/inward/record.url?scp=77649184125&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77649184125&partnerID=8YFLogxK

U2 - 10.1016/j.cca.2009.12.021

DO - 10.1016/j.cca.2009.12.021

M3 - Article

C2 - 20080080

AN - SCOPUS:77649184125

SN - 0009-8981

VL - 411

SP - 486

EP - 493

JO - Clinica Chimica Acta

JF - Clinica Chimica Acta

IS - 7-8

ER -