Paraoxonase 1 activities and genetic variation in childhood obesity

Abstract

Changes in paraoxonase 1 (PON1) activities have been observed in a variety of diseases involving oxidative stress, such as CVD. However, its role in obesity has not been fully established. In the present study, we aimed (1) to genotype sixteen PON1 SNP, (2) to measure serum PON1 activities and (3) to correlate these findings with the incidence of childhood obesity and related traits. We conducted a case-control study of 189 normal-weight and 179 obese prepubertal children, and we measured four different PON1 activities: lactonase; paraoxonase; arylesterase; diazoxonase. Although none of these activities was significantly different between the obese and normal-weight children, lactonase activity was found to be positively correlated with HDL-cholesterol and ApoA1 levels and negatively correlated with myeloperoxidase and fatty acid-binding protein 4 levels. Among the sixteen genotyped PON1 SNP, only the intronic SNP rs854566 exhibited a significant association with obesity (OR 0·61, 95 % CI 0·41, 0·91; P¼ 0·016). This genetic variant was also associated with increased diazoxonase, lactonase and arylesterase activities and decreased paraoxonase activity. Other genetic variants exhibited different association patterns with serum activities based on their location within the PON1 gene, and SNP that were located within the promoter were strongly associated with lactonase, arylesterase and diazoxonase activities. The functional variant Q192R exhibited the greatest effect on paraoxonase activity (P¼5·88 £ 10 242). In conclusion, SNP rs854566 was negatively associated with childhood obesity and with increased serum PON1 activities in prepubertal children. We determined that lactonase is a reliable indicator of PON1 activities and should be included in future studies of PON1 function.

Low Serum Paraoxonase-1 Lactonase and Arylesterase Activities in Obese Children and Adolescents

“…Moreover, while δ-valerolactone and phenyl acetate bind in a similar fashion to the PON1 active site and use the same catalytic mechanism, the hydrolysis of paraoxon (an aromatic phosphotriester) and of dihydrocoumarin (an aromatic lactone) uses distinctive parts of the active site network, therefore the binding and catalytic mechanisms are dissimilar (3). All the above could explain the Ar.ase and Lct.ase behavior observed in our study, and the unchanged Po.ase and Lct.ase reported by Ruperez et al (25) in the obese group.…”

“…In obese adults, both low (18)(19)(20)(21) or unchanged levels of Po.ase and Ar.ase (22) have been reported. Similarly, in obese children and adolescents, either low (11,23,24), unaffected levels of Po.ase and Ar.ase (25)(26)(27) or incresed levels of Ar.ase (28) have also been observed. Recently, unchanged (25) or reduced (14) levels of Lct.ase activity (assayed with dihydrocoumarin and 5-thiobutyl butyrolactone, respectively) have been reported in obese children.…”

Association between paraoxonase 1 (PON1) enzyme activity, PON1 C(−107)T polymorphism, nutritional status, and lipid profile in children

“…The association between excess weight in childhood and PON1 SNPs is still poorly investigated [23,24]. In particular, the association of PON1 C(−107)T and the nutritional status of children have been not studied yet.…”

Out-of-mind Inhibitors Of Human Serum Paraoxonase 1 (PON1): An In Vitro study

“…It has been demonstrated by studies that the paraoxonase1 (PON1) enzyme is related to the inhibition of lipid peroxidation of high-density lipoprotein cholesterol (HDL-C), reduced oxidative modification of lowdensity lipoprotein cholesterol (LDL-C) [15,16], and protection of HDL-C and LDL-C function [17,18]. Serum PON1 activity is an inversely proportional to CVD in that individuals with diseases of the carotid artery or coronary and myocardial infarction display lower PON1 activity [14,15].…”

“…Serum PON1 activity is an inversely proportional to CVD in that individuals with diseases of the carotid artery or coronary and myocardial infarction display lower PON1 activity [14,15]. Thus, PON1 has been detected as a candidate gene that may explain individual propensity for CVD [16,17].…”