Genotype and phenotype of salt-stimulated paraoxonase 1 (PON1) is associated with atherogenic indices in type 2 diabetes

  • Durdi Qujeq
  • Abdolkarim Mahrooz
  • Ahad Alizadeh
  • Parisa Masoumi
  • Saleh Annemohammadzadeh
  • Ruzbeh Boorank
Research Article



Paraoxonase 1 (PON1) and lipid abnormalities contribute to the development of cardiovascular disease, which is the principal cause of mortality in patients with type 2 diabetes (T2D). Data are not available on the potential association between salt-stimulated activity of PON1 (PON1-salt) and the atherogenic indices in T2D, therefore, we focused on these associations and evaluated whether the functional variants PON1-Q192R and PON1-L55M influence the associations.


Paraoxonase activity (PON1-para), arylesterase activity (PON1-aryl) and salt-stimulated activity (PON1-salt) were measured by spectrophotometric assays. The atherogenic index of plasma (AIP) was calculated from the log (TG/HDL-C). The genetic analyses were made by the restricted fragment length polymorphism after PCR amplification.


We observed that PON1-salt was negatively correlated with total cholesterol (TC)/HDL-C (r = −0.441,p = 0.006), LDL-C/HDL-C (r = −0.415, p = 0.011), and AIP (r = −0.422, p = 0.009). Correlations between PON1-salt and all three atherogenic indices were significantly affected by PON1-L55M and PON1-Q192R. Linear regression showed that AIP (p = 0.002), LDL-C/HDL-C (p = 0.005), and TC/HDL-C (p = 0.002) were independently associated with PON1-salt. Based on Ridge regression, the standardized coefficients −0.358, −0.297, and − 0.044 were obtained for AIP, LDL-C/HDL-C, and TC/HDL-C, respectively, and this shows that AIP could have more negative effect on PON1-salt than the others.


The decreased PON1-salt may be considered as a risk factor for atherosclerosis in T2D, therefore, understanding the associations between PON1-salt as an important although neglected property and atherogenic indices may be valuable in T2D. Accordingly, detection of PON1-salt status (phenotype and genotype) together with the atherogenic indices particularly AIP could be beneficial in identifying the increased atherogenicity in T2D.


Paraoxonase 1 PON1 Salt-stimulated activity Atherosclerosis Atherogenic index of plasma Type 2 diabetes 



Angiotensin-converting enzyme


Atherogenic index of plasma


Alanine aminotransferase


Coronary heart disease


Cardiovascular disease


Fractional esterification rate of HDL


Fasting plasma glucose


High density lipoprotein


Low density lipoproteins


Paraoxonase 1


Arylesterase activity of PON1


Paraoxonase activity of PON1


Salt-stimulated activity of PON1


Predicted residual error sum of squares


Restriction fragment length polymorphism


Single nucleotide variant


Total cholesterol


Type 2 diabetes




Variance inflation factors


Author’s contributions

A.M. obtained the funding, contributed to the design and conduct of the study, interpretation of data and writing of the manuscript. D.Q. contributed to study design, clinical interpretation, reviewed the manuscript, and contributed to the discussion. A.A. contributed to the statistical analysis, and reviewed and edited the manuscript. P.M., S.A., and R.B. contributed to study design, researched and analyzed data, and performed the experiments. All authors drafted the manuscript and gave final approval.

Compliance with ethical standards

Ethics approval

The study protocol was approved by the review committee and the Ethical committee at Mazandaran University of Medical Sciences.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.


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Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Cellular and Molecular Biology Research Center (CMBRC)Health Research Institute, Babol University of Medical SciencesBabolIran
  2. 2.Molecular and Cell Biology Research CenterMazandaran University of Medical SciencesSariIran
  3. 3.Immunogenetics Research CenterMazandaran University of Medical SciencesSariIran
  4. 4.Department of Clinical Biochemistry and Genetics, Faculty of MedicineMazandaran University of Medical SciencesSariIran
  5. 5.Department of Epidemiology and Reproductive Health, Reproductive Epidemiology Research CenterRoyan Institute for Reproductive Biomedicine, ACECRTehranIran

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