Paraoxonase 1 status in the Thai population

Abstract

Human serum paraoxonase 1 (PON1), a highdensity lipoprotein (HDL)-associated enzyme, has been shown to reduce the oxidation of low-density lipoprotein (LDL) and HDL by degrading lipid peroxides. This property of PON1 accounts for its ability to protect against atherosclerosis. In this study, we identified four polymorphisms in both the coding (L55M and Q192R) and regulatory regions (T-108C and G-909C) of the human PON1 gene in 202 healthy Thai individuals and investigated the influence of these polymorphisms on serum PON1 activity towards three substrates, namely, paraoxon, phenylacetate and diazoxon. The PON1 L55M, Q192R and G-909C polymorphisms significantly affected the variation in serum PON1 activity towards paraoxon. Serum PON1 activity towards paraoxon was significantly different among the genotype groups, as follows: 55LL > 55LM/55MM, 192RR > 192QR > 192QQ and À909CC > À909CG > À909GG. The PON1 Q192R and G-909C polymorphisms also influenced the variation in serum PON1 activity towards diazoxon but in the opposite direction to the activity towards paraoxon. Only the PON1 L55M polymorphism was associated with significant variation in serum PON1 activity towards phenylacetate while the PON1 T-108C polymorphism had no significant effect on serum PON1 activity towards any substrate. We also found linkage disequilibrium among the polymorphic sites, including Q192R versus L55M, Q192R versus T-108C and Q192R versus G-909C. Serum PON1 activity towards both paraoxon and phenylacetate, but not diazoxon, was positively correlated with HDL cholesterol (HDL-C) and apo AI concentrations. None of the PON1 polymorphisms significantly affected serum lipid, lipoprotein or apolipoprotein concentrations. Our findings suggest that the physiological relevance of the PON1 polymorphisms is that they are associated with significant differences in serum PON1 activity, and the impact of PON1 polymorphisms on this activity is substrate-dependent.

Genotype and phenotype frequencies of paraoxonase 1 in fertile and infertile men

“…This enzyme has two distinct activities, i.e., paraoxonase and arylesterase and each of these activities reflects a unique genotype [Furlong et al 1988;Gaidukov et al 2006;Phuntuwate et al 2005]. In accordance with the data above, we can conclude that the BB phenotype is not affected by the QQ, QR, or RR genotypes.…”

Paraoxonase 1 and Its Relationship With Pesticide Biomarkers in Indigenous Mexican Farmworkers

“…39,[54][55][56][57] In this study, a wide variation in PON1 activity among individuals was observed; a variability of 6.17-fold was observed when phenylacetate was used as a substrate, and a 4.4-fold variability was observed with substrate CMPA. Although a large interindividual variation in PON1 activity was observed in this work, there is actually less variation in this indigenous population compared with others.…”

“…Our results agree with previous studies that reveal interpopulation differences in allele frequencies for the PON1 polymorphisms, and support the hypothesis that indigenous Amerindians and Asians share a common ancestral origin, perhaps the reason why populations from America and Asia demonstrate strong genetic affinities. 37,[55][56][57]63 Given the role of PON1 in pesticide toxicity, 64 it is not surprising that particular attention has been devoted to factors that may modulate PON1 activity or expression. 10,67,68 An individual's plasma PON1 activity toward a particular substrate can be predicted by PON1 polymorphisms in both the coding and regulatory regions, 64,32 and may also be modulated by environmental factors including pes- 26,36,55,63 Our finding that no significant variation in AREase activity was associated with specific PON1 M155L or Q192R polymorphisms was in agreement with previous studies.…”

Biochemical, Environmental, and Genetic Factors Associated with Paraoxonase (PON1) Activity

“…The PON1 activity was determined using paraoxon (diethyl p-nitrophenyl phosphate) and phenyl acetate (Phuntuwate et al 2005). Paraoxon hydrolytic activity was measured by a continuous spectrophotometer at 405 nm at 25°C for 3 min and expressed as nmol of 4-nitrophenol formed per minute per ml (nmol/min/ ml).…”