Genotype and phenotype of salt-stimulated paraoxonase 1 (PON1) is associated with atherogenic indices in type 2 diabetes
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.
KeywordsParaoxonase 1 PON1 Salt-stimulated activity Atherosclerosis Atherogenic index of plasma Type 2 diabetes
Atherogenic index of plasma
Coronary heart disease
Fractional esterification rate of HDL
Fasting plasma glucose
High density lipoprotein
Low density lipoproteins
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
Type 2 diabetes
Variance inflation factors
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
The study protocol was approved by the review committee and the Ethical committee at Mazandaran University of Medical Sciences.
Consent for publication
The authors declare that they have no competing interests.
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