Effects of Intronic and Exonic Polymorphisms of Paraoxonase 1 (PON1) Gene on Serum PON1 Activity in a Korean Population

Paraoxonase 1 (PON1) hydrolyzes a number of toxic organophosphorous compounds and reduces lipid peroxide accumulation, and PON1 genetic polymorphisms in the coding region modulate serum PON1 activity. In this study, we investigated the association between 3 polymorphisms of PON1 located in intron 5 (17899insdelTT and 17974CT) and exon 6 (192QR) and serum PON1 activity. The genetic polymorphisms and serum activity of PON1 were analyzed in 153 healthy Koreans by using a direct sequencing assay and spectrophotometric method, respectively. A significant linkage disequilibrium (LD) was observed between all tested single nucleotide polymorphisms, with the strongest LD observed between 17899insdelTT and 192QR (D' = 0.984). The 17899insdelTT, 17974CT and 192QR genetic polymorphisms were associated with significant differences in serum paraoxonase activity. In multiple regression analyses, smoking, triglyceride level, high-density lipoprotein (HDL) level, and the 17899insdelTT and 192QR genetic polymorphisms were significant determinants of serum paraoxonase activity, while age, smoking, triglyceride level, HDL level, and the 192QR genetic polymorphism were significant determinants of serum arylesterase activity. These results suggest that although the 192QR genetic polymorphism in the coding region of PON1 is primarily associated with serum PON1 activity, the intronic polymorphisms are also involved in serum PON1 activity, and this association may be mediated by LD.

Proatherogenic or antiatherogenic high density lipoprotein type in acute coronary syndrome and healthy male person.

Aim: To make proatherogenic/antiatherogenic HDL type criteria using Apolipoprotein A-I (ApoA-I), Paraoxonase-1 (PON-1), Neopterin and HDL-cholesterol levels, which may be useful in clinical practice. Methods: This was a case control study recruiting 52 subjects with Acute Coronary Syndrome (ACS) and 30 control healthy subjects. HDL type was classifi ed into antiatherogenic and proatherogenic based on the levels of ApoA-I, PON-1, Neopterin and HDL-cholesterol. Concentrations of ApoA-I was measured by immunoturbidimetry method, PON-1 was measured by colorimetric method, Neopterin was measured by ELISA, and HDL-C was determined by homogenous method. Univariate logistic regression analysis was done using ACS as a dependent variable and levels of ApoA-I, PON-1, Neopterin and HDL-cholesterol as independent variables. Proatherogenic/antiatherogenic HDL type was determined by using ApoA-I, PON-1, Neopterin and HDL-cholesterol cut off and odd ratios. Results: Patient’s age was 50.89 + 12.63 year, HDL-C was 39.82 + 9.84 mg/dL, Apo A-1 was 119.77 + 32.05 mg/ dL, PON-1 was 41.26 + 18.19 kU/L, Neopterin was 16.22 + 38.10 nmol/L. Cut offs of ApoA-I, PON-1 and Neopterin successively were 124.5 mg/dL, 40.8 kU/L, and 7.016 nmol/L. On univariate logistic regression analysis showed that OR of ApoA-I, PON-1 and Neopterin respectively were 29.759 (95% CI : 4.074 – 217.382), 1.647 (95% CI : 0.412 – 6.586), 4.317 (95% CI : 1.098 – 16.977). Using scoring system, we concluded that total score > 18 was proatherogenic HDL type, and total score < 18 was antiatherogenic HDL type. With this scoring we found 78.85% had proatherogenic HDL type in ACS population. Conclusions: Dysfunctional HDL or proatherogenic/antiatherogenic HDL type can be predicted by using ApoA-I – PON-1 – Neopterin – HDL-cholesterol scoring system. Those with score of 18 are supposed to have antiatherogenic HDL type, and those with score of > 18 were having proatherogenic HDL type.