Skip to main content
Log in

Low human paraoxonase predicts cardiovascular events in Japanese patients with type 2 diabetes

  • Short Communication
  • Published:
Acta Diabetologica Aims and scope Submit manuscript

Abstract

Human serum paraoxonase (PON1) is associated with HDL and inhibits oxidative modification of LDL. PON1 enzymatic activity has been shown to decrease in diabetic patients; however, the effect of PON1 status on long-term outcome has not been reported. In this study, we examined the association between baseline PON1 status and the development of cardiovascular disease (CVD) during 10 years of follow-up in 88 type 2 diabetic patients whose enzymatic activities, concentrations, and genetic polymorphisms of PON1 had been determined. A total of 20 CVD events were recorded during the follow-up period. Using Kaplan–Meier survival curves, we found a significantly increased incidence of CVD in patients with a lower concentration or paraoxonase activity of PON1 than each median value (log-rank 7.460; < 0.01, and log-rank 4.187; < 0.05, respectively). By Cox regression analysis, both concentration and paraoxonase activity were significantly associated with the development of CVD, even after correction for gender, age, and preexisting CVD (P < 0.05). Low concentration and enzymatic activity of PON1 may be an independent predictor of cardiovascular events in diabetic patients.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1

References

  1. Mackness MI, Arrol S, Abbott C, Durrington PN (1993) Protection of low-density lipoprotein against oxidative modification by high-density lipoprotein associated praoxonase. Atherosclerosis 104:129–135

    Article  PubMed  CAS  Google Scholar 

  2. Ikeda Y, Suehiro T, Inoue M, Nakauchi Y, Morita T, Arii K, Ito H, Kumon Y, Hashimoto K (1998) Serum paraoxonase activity and its relationship to diabetic complications in patients with non-insulin-dependent diabetes mellitus. Metabolism 47:598–602

    Article  PubMed  CAS  Google Scholar 

  3. Inoue M, Suehiro T, Nakamura T, Ikeda Y, Kumon Y, Hashimoto K (2000) Serum arylesterase/diazoxonase activity and genetic polymorphisms in patients with type 2 diabetes. Metabolism 49:1400–1405

    Article  PubMed  CAS  Google Scholar 

  4. Mackness B, Mackness MI, Arrol S, Turkie W, Julier K, Abuasha B, Miller JE, Boulton AJM, Durrington PN (1998) Serum paraoxonase (PON1) 55 and 192 polymorphism and paraoxonase activity and concentration in non-insulin dependent diabetes mellitus. Atherosclerosis 139:341–349

    Article  PubMed  CAS  Google Scholar 

  5. Boemi M, Leviev I, Sirolla C, Pieri C, Marra M, James RW (2001) Serum paraoxonase is reduced in type 1 diabetic patients compared to non-diabetic, first degree relatives; influence on the ability of HDL to protect LDL from oxidation. Atherosclerosis 155:229–235

    Article  PubMed  CAS  Google Scholar 

  6. Lakshman MR, Gottipati CS, Narasimhan SJ, Munoz J, Marmillot P, Nylen ES (2006) Inverse correlation of serum paraoxonase and homocysteine thiolactonase activities and antioxidant capacity of high-density lipoprotein with the severity of cardiovascular disease in persons with type 2 diabetes mellitus. Metabolism 55:1201–1206

    Article  PubMed  CAS  Google Scholar 

  7. McElveen J, Mackness MI, Colley CM, Peard T, Warner S, Walker CH (1986) Distribution of paraoxon hydrolytic activity in the serum of patients after myocardial infarction. Clin Chem 32:671–673

    PubMed  CAS  Google Scholar 

  8. Ayub A, Mackness MI, Arrol S, Mackness B, Patel J, Durrington PN (1999) Serum paraoxonase after myocardial infarction. Arterioscler Thromb Vasc Biol 19:330–335

    PubMed  CAS  Google Scholar 

  9. Kim NS, Kang K, Cha MH, Kang B-J, Moon J, Kang BK, Yu B-C, Kim Y-S, Choi SM, Bang O-S (2007) Decreased paraoxonase-1 activity is a risk factor for ischemic stroke in Koreans. Biochem Biophys Res Commun 364:157–162

    Article  PubMed  CAS  Google Scholar 

  10. Can Demirdögen B, Türkanoglu A, Bek S, Sanisoglu Y, Demirkaya S, Vural O, Arınc E, Adalı O (2008) Paraoxonase/arylesterase ratio, PON1 192Q/R polymorphism and PON1 status are associated with increased risk of ischemic stroke. Clin Biochem 41:1–9

    Article  PubMed  Google Scholar 

  11. Bhattacharyya T, Nicholls SJ, Topol EJ, Zhang R, Yang X, Schmitt D, Fu X, Shao M, Brennan DM, Ellis SG, Brennan M-L, Allayee H, Lusis AJ, Hazen SL (2008) Relationship of paraoxonase 1 (PON1) gene polymorphisms and functional activity with systemic oxidative stress and cardiovascular risk. JAMA 299:1265–1276

    Article  PubMed  CAS  Google Scholar 

  12. Durrington PN, Mackness B, Mackness MI (2001) Paraoxonase and atherosclerosis. Arterioscler Thromb Vasc Biol 21:473–480

    PubMed  CAS  Google Scholar 

  13. Wheeler JG, Keavney BD, Watkins H, Collins R, Danesh J (2004) Four paraoxonase gene polymorphisms in 11212 cases of coronary heart disease and 12786 controls: meta-analysis of 43 studies. Lancet 363:689–695

    Article  PubMed  CAS  Google Scholar 

  14. Mackness B, Mackness MI, Arrol S, Turkie W, Durrington PN (1998) Effect of the human serum paraoxoanse 55 and 192 genetic polymorphisms on the protection by high density lipoprotein against low density lipoprotein oxidative modification. FEBS Lett 423:57–60

    Article  PubMed  CAS  Google Scholar 

  15. Kotur-Stevuljevic J, Spasic S, Jelic-Ivanovic Z, Spasojevic-Kalimanovska V, Stefanovic A, Vujovic A, Memon L, Kalimanovska-Ostric D (2008) PON1 status is influenced by oxidative stress and inflammation in coronary heart disease patients. Clin Biochem 41:1067–1073

    Article  PubMed  CAS  Google Scholar 

  16. Robertson KS, Hawe E, Miller GJ, Talmud PJ, Humphries SE (2003) Human paraoxonase gene cluster polymorphisms as predictors of coronary heart disease risk in the prospective Northwick Park Heart Study II. Biochim Biophys Acta 1639:203–212

    PubMed  CAS  Google Scholar 

  17. Turban S, Fuentes F, Ferlic L, Brugada R, Gotto AM, Ballantyne CM, Marian AJ (2001) A prospective study of paraoxonase gene Q/R192 polymorphism and severity, progression and regression of coronary atherosclerosis, plasma lipid levels, clinical events and response to fluvastatin. Atherosclerosis 154:633–640

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yukio Ikeda.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ikeda, Y., Inoue, M., Suehiro, T. et al. Low human paraoxonase predicts cardiovascular events in Japanese patients with type 2 diabetes. Acta Diabetol 46, 239–242 (2009). https://doi.org/10.1007/s00592-008-0066-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00592-008-0066-3

Keywords

Navigation