Paraoxonase1 status in healthy Thai population and effect of Fenofibrate therapy on paraoxonase 1 status in patients with low high-density lipoprotein cholesterol levels

• Main Author: Wimon Phuntuwate
• Other Authors: Chuthamanee Suthisisang
• Language: English
• Published: Mahidol University. Mahidol University Library and Knowledge Center 2023
• Subjects: Lipoproteins, HDL Cholesterol > drug effects; Polymorphism (Pharmacy); Procetofen > therapeutic use; Triglycerides > drug effects
• Online Access: https://repository.li.mahidol.ac.th/handle/123456789/88663
• Institution: Mahidol University

The aims of this study are to determine the PON1 polymorphisms and to investigate the influence of these polymorphisms on serum PON1 concentration and PON1 activity in healthy Thais. In addition, the effect of fenofibrate on PON1 levels and the influence of these PON1 polymorphisms on the therapeutic response of fenofibrate in patients with low HDL-C levels was also investigated. In healthy Thais, genotype and allele frequencies of the PON1 L55M, Q192R, T-108C and G-909C polymorphisms were 89.55%LL, 10.45%LM (L=0.95, M=0.05), 50.0%QQ, 41.79%QR, 8.21%RR (Q=0.71, R=0.29), 55.22%TT, 41.05%CT, 3.73%CC (T=0.76, C=0.24), 55.22%CC, 34.33%CG, and 10.45%GG (C=0.72, G=0.28), respectively. The PON1 L55M polymorphism was associated with a significant variation in serum PON1 concentration. The levels of PON1 activity towards paraoxon and diazoxon were significantly influenced by the PON1 Q192R and G-909C polymorphisms. These findings indicate the physiological relevance of the PON1 polymorphisms in healthy Thais since they are associated with significant differences in serum PON1 levels. Fenofibrate significantly decreased triglycerides, non-HDL-C, oxidized LDL and apo B levels whereas HDL-C and apo AI levels were significantly increased. Interestingly, there were significant increases in both PON1 concentration and activity. The therapeutic response of lipid parameters to fenofibrate was independent of PON1 polymorphisms whereas the PON1 Q192R and T-108C polymorphisms affected the therapeutic response of PON1 levels to fenofibrate therapy. The 192QQ and -108TT genotypes had higher increase in PON1 levels in response to fenofibrate. Fenofibrate treatment in patients with low HDL-C levels not only reduces atherogenic lipids and increases atheroprotective lipids but also increases PON1 levels. Increasing PON1 levels by fenofibrate may play an important role in decreasing LDL oxidation.