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 (η²= 0.127, P = 0.002 for PON1–Q192R; η²= 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.