Effect of fenofibrate therapy on paraoxonase1 status in patients with low HDL-C levels.
OBJECTIVE
We evaluated the effect of micro-coated fenofibrate on lipid parameters, high sensitivity C-reactive protein and paraoxonase1 levels in dyslipidemic patients with low high-density lipoproteins levels. In addition, the effects of the paraoxonase1 polymorphisms on lipid and paraoxonase1 responses to fenofibrate therapy were examined.


METHODS
A total of 61 dyslipidemic patients with low high-density lipoproteins levels were recruited into this study to receive micro-coated fenofibrate (160 mg/day) for 12 weeks. Lipid parameters, C-reactive protein, paraoxonase1 concentration and activity were measured at baseline and after 6 and 12 weeks of fenofibrate treatment. Four polymorphisms in both the coding (L55M and Q192R) and regulatory regions (T-108C and G-909C) of human paraoxonase1 were also quantified.


RESULTS
Micro-coated fenofibrate significantly decreased total cholesterol, triglycerides, non-high-density lipoprotein cholesterol, oxidized low-density lipoprotein and apolipoprotein-B levels after 6 and 12 weeks (all p<0.001). While high-density lipoprotein and apolipoprotein AI levels were significantly increased by 14.7% and 6.9%, respectively, after 6 weeks and by 17.3% and 7.2%, respectively, after 12 weeks (all p<0.01). There were no significant differences in the mean of low-density lipoprotein and C-reactive protein after fenofibrate treatment. There were significant increases in paraoxonase1 concentration and activity by 7.7% and 5.7% after 6 weeks and by 14.6% and 10.1% after 12 weeks, respectively (all p<0.01). After micro-coated fenofibrate therapy, a significantly positive correlation between the change in high-density lipoprotein and the changes in paraoxonase1 concentration and activity was observed (p=0.001). On the other hand, the changes in paraoxonase1 activity were significantly and negatively correlated with the changes in triglycerides (p=0.007). The therapeutic response of lipid parameters to micro-coated fenofibrate was independent of paraoxonase1 polymorphisms. However, paraoxonase1 Q192R and T-108C polymorphisms significantly affected the increase in paraoxonase1 activity (the highest increase in 192QQ and -108TT) and paraoxonase1 concentration (the highest increase in -108TT).


CONCLUSIONS
Lipid-modifying therapy with micro-coated fenofibrate in patients with low high-density lipoprotein levels not only reduced atherogenic lipids (total cholesterol, triglycerides, oxidized low-density lipoprotein and apolipoprotein-B) and increased atheroprotective lipids but also increased paraoxonase1 concentration and activity. Increasing paraoxonase1 levels by fenofibrate may play an important role in decreasing low-density lipoprotein oxidation.
Phuntuwate
Wimon
W
Department of Pharmacology, Faculty of Pharmacy, Mahidol University, Sri Ayudhaya Road, Bangkok 10400, Thailand.
Suthisisang
Chuthamanee
C
Department of Pharmacology, Faculty of Pharmacy, Mahidol University, Sri Ayudhaya Road, Bangkok 10400, Thailand. Electronic address: pycst@mahidol.ac.th.
Koanantakul
Banhan
B
Cardiac and Preventive Center, Bhumibol Adulyadej Hospital, Bangkok 10200, Thailand.
Chaloeiphap
Preecha
P
Division of Preventive Medicine, Royal Thai Air Force, Bangkok 10200, Thailand.
Mackness
Bharti
B
University of Manchester, Department of Medicine, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK.
Mackness
Mike
M
University of Manchester, Department of Medicine, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK.
D000328:Adult; D043303:Aryldialkylphosphatase / Q000187:drug effects* / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood / Q000187:drug effects; D011345:Fenofibrate / Q000494:pharmacology*; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D006949:Hyperlipidemias / Q000188:drug therapy; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000187:drug effects* / Q000235:genetics
D008076:Cholesterol, HDL; D000960:Hypolipidemic Agents; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; D011345:Fenofibrate