Skip to main content
SpringerLink
Log in

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

  • Published:
Journal of Thrombosis and Thrombolysis Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Caslake MJ, Packard CJ, Suckling KE et al (2000) Lipoprotein-associated phospholipaseA(2), platelet-activating factor acetylhydrolase: a potential new risk factor for coronary artery disease. Atherosclerosis 150:413–419

    Article  PubMed  CAS  Google Scholar 

  2. Ishihara M, Iwasaki T, Nagano M et al (2004) Functional impairment of two novel mutations detected in lipoprotein-associated phospholipase A2 (Lp-PLA2) deficiency patients. J Hum Genet 49:302–307

    Article  PubMed  CAS  Google Scholar 

  3. Yamada Y, Yoshida H, Ichihara S et al (2000) Correlation between plasma platelet activating factor acetylhydrolase (PAF-AH) activity and PAF-AH genotype, age, and atherosclerosis in a Japanese population. Atherosclerosis 150:209–216

    Article  PubMed  CAS  Google Scholar 

  4. Jang Y, Kim OY, Koh SJ et al (2006) The Val279Phe variant of the lipoprotein- associatedphospholipase A2 gene is associated with catalytic activities and cardiovascular disease in Korean men. J Clin Endocrinol Metab 91:3521–3527

    Article  PubMed  CAS  Google Scholar 

  5. Kruse S, Mao XQ, Heinzmann A et al (2000) The Ile198Thr and Ala379Val variants of plasmatic PAF-acetylhydrolase impair catalytical activities and are associated with atopy and asthma. Am J Hum Genet 66:1522–1530

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  6. Ninio E, Tregouet D, Carrier JL et al (2004) Platelet-activating factor-acetylhydrolase and PAF-receptor gene haplotypes in relation to future cardiovascular event in patients with coronary artery disease. Hum Mol Genet 13:1341–1351

    Article  PubMed  CAS  Google Scholar 

  7. Hoffmann MM, Winkler K, Renner W et al (2009) Genetic variants and haplotypes of lipoprotein associated phospholipase A2 and their influence on cardiovascular disease (The Ludwigshafen Risk and Cardiovascular Health Study). J Thromb Haemost 7:41–48

    Article  PubMed  CAS  Google Scholar 

  8. Liu PY, Li YH, Wu HL et al (2006) Platelet-activating factor-acetylhydrolase A379V (exon11) gene polymorphism is an independent and functional risk factor for premature myocardial infarction. J Thromb Haemost 4:1023–1028

    Article  PubMed  CAS  Google Scholar 

  9. Wootton PT, Stephens JW, Hurel SJ et al (2006) Lp-PLA2 activity and PLA2G7 A379V genotype in patients with diabetes mellitus. Atherosclerosis 189:149–156

    Article  PubMed  CAS  Google Scholar 

  10. Abuzeid AM, Hawe E, Humphries SE et al (2003) Association between the Ala379Val variant of the lipoprotein associated phospholipase A2 and risk of myocardial infarction in the north and south of Europe. Atherosclerosis 168:283–288

    Article  PubMed  CAS  Google Scholar 

  11. Casas JP, Ninio E, Panayiotou A et al (2010) PLA2G7 genotype, lipoprotein-associated phospholipase A2 activity, and coronary heart disease risk in 10 494 cases and 15 624 controls of European Ancestry. Circulation 121:2284–2293

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  12. Jeong TS, Kim MJ, Yu H et al (2005) (E)-Phenyl- and -heteroaryl-substituted O-benzoyl-(or acyl)oximes as lipoprotein-associated phospholipase A2 inhibitors. Bioorg Med Chem Lett 15:1525–1527

    Article  PubMed  CAS  Google Scholar 

  13. Zalewski A, Macphee C (2005) Role of lipoprotein-associated phospholipase A2 in atherosclerosis. Arterioscler Thromb Vasc Biol 25:923–931

    Article  PubMed  CAS  Google Scholar 

  14. Stafforini DM, Sheller JR, Blackwell TS et al (2006) Release of free F2-isoprostanes from esterified phospholipids is catalyzed by intracellular and plasma platelet-activating factor acetylhydrolases. J Biol Chem 281:4616–4623

    Article  PubMed  CAS  Google Scholar 

  15. Morrow JD (2005) Quantification of isoprostanes as indices of oxidant stress and the risk of atherosclerosis in humans. Arterioscler Thromb Vasc Biol 25:279–286

    Article  PubMed  CAS  Google Scholar 

  16. Cottone S, Mulè G, Nardi E et al (2007) C-reactive protein and intercellular adhesion molecule-1 are stronger predictors of oxidant stress than blood pressure in established hypertension. J Hypertens 25:423–428

    Article  PubMed  CAS  Google Scholar 

  17. Kals J, Kampus P, Kals M et al (2008) Inflammation and oxidative stress are associated differently with endothelial function and arterial stiffness in healthy subjects and in patients with atherosclerosis. Scand J Clin Lab Invest 68:594–601

    Article  PubMed  CAS  Google Scholar 

  18. Zhu Y, Lin JH, Liao HL et al (1997) Activation of ICAM-1 promoter by lysophosphatidyl choline: possible involvement of protein tyrosine kinases. Biochim Biophys Acta 1345:93–98

    Article  PubMed  CAS  Google Scholar 

  19. Ridker PM, Hennekens CH, Roitman-Johnson B et al (1998) Plasma concentration of soluble intercellular adhesion molecule 1 and risks of future myocardial infarction in apparently healthy men. Lancet 351:88–92

    Article  PubMed  CAS  Google Scholar 

  20. Hwang SJ, Ballantyne CM, Sharrett AR et al (1997) Circulating adhesion molecules VCAM-1, ICAM-1, and E-selectin in carotid atherosclerosis and incident coronary heart disease cases: the atherosclerosis risk in communities (ARIC) study. Circulation 96:4219–4225

    Article  PubMed  CAS  Google Scholar 

  21. De Lemos JA, Hennekens CH, Ridker PM et al (2000) Plasma concentration of soluble vascular cell adhesion molecule-1 and subsequent cardiovascular risk. J Am Coll Cardiol 36:423–426

    Article  PubMed  Google Scholar 

  22. Malik I, Danesh J, Whincup P et al (2001) Soluble adhesion molecules and prediction of coronary heart disease: a prospective study and meta-analysis. Lancet 358:971–976

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank the research volunteers who participated in the studies described in this article. This research was supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2006-2005306, 2010-0015017, and 2012M3A9C4048762).

Author information

Authors and Affiliations

  1. Yonsei University Research Institute of Science for Aging, Yonsei University, Seoul, Korea

    Jey Sook Chae, Jung Hyun Kwak & Jong Ho Lee

  2. National Leading Research Laboratory of Clinical Nutrigenetics/Nutrigenomics, Department of Food and Nutrition, College of Human Ecology, Yonsei University, Seoul, Korea

    Minjoo Kim, Kyoung Hun Shin & Jong Ho Lee

  3. Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-749, Korea

    Minjoo Kim & Jong Ho Lee

  4. Department of Family Practice, National Health Insurance Corporation Ilsan Hospital, Goyang, Korea

    Sang-Hyun Lee

  5. National Research Laboratory of Lipid Metabolism and Atherosclerosis, Korea Research Institute of Bioscience and Biotechnology, Daejon, Korea

    Tae-Sook Jeong

Authors
  1. Jey Sook Chae
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jung Hyun Kwak
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Minjoo Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kyoung Hun Shin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sang-Hyun Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tae-Sook Jeong
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jong Ho Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jong Ho Lee.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 60 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chae, J.S., Kwak, J.H., Kim, M. et al. Effects of A379V variant of the Lp-PLA 2 gene on Lp-PLA2 activity and markers of oxidative stress and endothelial function in Koreans. J Thromb Thrombolysis 38, 477–484 (2014). https://doi.org/10.1007/s11239-014-1074-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11239-014-1074-5

Keywords

Search

Navigation