Paraoxonase 1 Activity and its Polymorphism in Type 2 Diabetic Nephropathy

Abstract

Objective: This study aims to investigate the role of paraoxonase 1 activity and Q192R polymorphism in the development of nephropathy in patients with Type 2 diabetes mellitus. Material and Methods: This case-control study included 100 patients with Type 2 diabetes mellitus for more than five years, admitted to our hospital. They were divided into two groups (with and without diabetic nephropathy) on the basis of albumin-creatinine ratio. Serum samples of all patients were subjected to paraoxonase 1 arylesterase activity, using phenylacetate as the substrate. Paraoxonase 1 phenotyping was carried out by calculating the ratio of inhibited arylesterase activity to non-inhibited arylesterase activity using phenylacetate and p-nitrophenyl acetate, respectively, as substrates. Results: Paraoxonase 1 arylesterase activity was found to be significantly lower in subjects with diabetic nephropathy than that in the subjects without diabetic nephropathy (85.4±24.12 vs. 127.94±25.51 p=0.01). Bothunivariate (Odds ratio=1.073, Neglekerke's R2=0.565, area under the curve=0.888, p≤0.001) and multivariate (Odds ratio= 1.067, [95% confidence interval (1.023-1.113), p=0.003)] logistic tests showed independent, protective association of paraoxonase 1 arylesterase activity with the development of diabetic nephropathy. Paraoxonase 1 RR homozygous diabetic patients were observed to be significantly associated with diabetic nephropathy in the univariate logistic regression (R2=0.056 area under the curve=0.600 p=0.037), while the multivariate analysis did not show any significance. Conclusion: A decreased paraoxonase 1 arylesterase activity may be considered to be an additional risk factor in the development of nephropathy in diabetes mellitus. Paraoxonase 1 RR homozygous individuals may be at an increased risk of being affected by diabetic nephropathy.

Association of NPHS2, PON1 and KCNJ11 Gene Polymorphisms with Diabetic Nephropathy

“…A study on South Indian population reported similar results that GG genotype could be a risk factor for DN. Furthermore, they also found decreased PON1 enzymatic activity in GG homozygotes as compared to AA homozygotes (Mogarekar et al 2018). Our study found AA genotype to have statistically insigni cant protective effect on DN.…”

The importance of paraoxonase 1 activity in chronic kidney disease

“…Thus, decreased levels of HDL-PON1 activity in patients with T2DM are plausibly indicative of incipient or overt nephropathy. Importantly, considering the advantages of measurement of arylesterase over paraoxonase activity, which has lower inter-individual variability and is minimally affected by PON1 polymorphisms, there were studies proposing arylestease and not paraoxonase PON1 as a biomarker for predicting the progression of CKD in T2DM [ 117 , 118 ].…”