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

doi:10.1007/s40200-018-0332-z

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

J Diabetes Metab Disord. 2018 Mar 26;17(1):1-10. doi: 10.1007/s40200-018-0332-z. eCollection 2018 Jun.

Authors

Durdi Qujeq¹, Abdolkarim Mahrooz^{2

3

4}, Ahad Alizadeh⁵, Parisa Masoumi⁴, Saleh Annemohammadzadeh⁴, Ruzbeh Boorank⁴

Affiliations

¹ 1Cellular and Molecular Biology Research Center (CMBRC), Health Research Institute, Babol University of Medical Sciences, Babol, Iran.
² 2Molecular and Cell Biology Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
³ 3Immunogenetics Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
⁴ 4Department of Clinical Biochemistry and Genetics, Faculty of Medicine, Mazandaran University of Medical Sciences, Km 17 Khazarabad Road, Sari, Iran.
⁵ 5Department of Epidemiology and Reproductive Health, Reproductive Epidemiology Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Atherogenic index of plasma; Atherosclerosis; PON1; Paraoxonase 1; Salt-stimulated activity; Type 2 diabetes.