The common variant Q192R at the paraoxonase 1 (PON1) gene and its activity are responsible for a portion of the altered antioxidant status in type 2 diabetes

Abstract

In this study, we investigated the effects of paraoxonase 1 (PON1) activities and the variant PON1-Q192R on the ferric reducing ability of plasma (FRAP) and total thiol. In addition, we examined the distribution of genotypes of this variant and the relationship of the genotypes with age in patients with type 2 diabetes (T2D). A total of 115 patients with T2D were enrolled in this study. Paraoxonase activity (PON-para) and arylesterase activity (PON-aryl) were determined using spectrophotometric assays. The distribution of the Q192R genotypes was determined by the double substrate method. The antioxidant status was evaluated by determining FRAP and total thiol. The frequencies of Q and R allozyme were 0.78 and 0.22, respectively. The multivariate analysis identified a significant association between the variables PON1-Q192R (Wilks' λ = 0.85, P = 0.002) and PON-aryl (Wilks' λ = 0.896, P = 0.017), with FRAP and total thiol. The significant difference observed for PON1-Q192R and PON-aryl is primarily due to the changes in FRAP levels (η(2 )= 0.127, P = 0.002 for PON1-Q192R; η(2 )= 0.083, P = 0.011 for PON-aryl). The interaction PON1-Q192R-PON-aryl increased the effect sizes from 8 to 19% for FRAP. Only in R-carrying genotypes, there were significant correlations between both PON-para/HDL (r = -0.574, P < 0.001) and PON-aryl/HDL (r = -0.577, P < 0.001) with age. Our data suggest that the variant PON1-Q192R and PON1 activity, particularly PON-aryl, influenced the antioxidant status in T2D. The interaction of this variant and PON1 activity increased the effect size on the antioxidant capacity. Moreover, the presence of the R allozyme may potentiate the effects of age on susceptibility to cardiovascular diseases in T2D.

The Role of PON1 Variants in Disease Susceptibility in a Turkish Population

“…In a study conducted on a group of individuals with cardiovascular disease, the G allele frequency of PON1 rs662 was higher in the patient group, but no statistically significant difference was found than the healthy individuals. 35 In another study, the relation between cardiovascular diseases and PON1 rs662 and rs854560 polymorphisms was investigated. The T allele frequency of PON1 rs854560 was higher in the patient group.…”

Evaluation of paraoxonase, arylesterase, and homocysteine thiolactonase activities in patients with diabetes and incipient diabetes nephropathy

“…High HTLase activity has been reported to provide better protection against protein homocysteinylation compared to low HTLase activity (7). Recent studies have demonstrated that PON-1 and ARE are enzymes in the esterase group that are encoded by the same gene and whose active centres are similar (14, 15). Although PON-1 is known to present polymorphic changes, ARE enzyme does not show any genetic polymorphism (16).…”

The Impact of Rs662 Genotyping on the Serum Activity of the Paraoxonase -1 Enzyme in Iraqi Patients With Cardiovascular Diseases.

“…Yet, higher frequencies of Q allozymes (0.78) was previously reported by Zargari et al (2016) Hernández-Díaz et al (2016) who revealed that the 192Q allele carriers are at high risk to develop CAD. On the other hand, in another study , Bounafaa et al (2015) reported that the PON1 R allele is abundant in CHD patients, indicating that the PON1192 polymorphism may be a risk factor for atherosclerosis.…”