Effect of paraoxonase 1 polymorphisms on the response of lipids and lipoprotein-associated enzymes to treatment with fluvastatin (Journal article)

Christidis, D. S./ Liberopoulos, E. N./ Kakafika, A. I./ Miltiadous, G. A./ Liamis, G. L./ Kakaidi, B./ Tselepis, A. D./ Cariolou, M. A./ Elisaf, M. S.


Background. Decreased paraoxonase 1 (PON1) and increased total serum lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) activities are suggested to be risk factors for vascular disease. Common PON1 genetic polymorphisms (Q192R and L55M) significantly affect PON1 activity and may also influence high-density lipoprotein (HDL)-associated Lp-PLA(2) activity. However, little is known about the possible effect of PON1 common genetic polymorphisms on the response of lipids as well as PON1 and Lp-PLA(2) activities to treatment with statins. Methods. Two hundred two hypercholesterolemic patients were treated with fluvastatin 40 mg/day. Fasting serum lipids, Q192R and L55M PON1 polymorphisms as well as PON1 and Lp-PLA(2) (total serum and HDL-associated) activities were determined before and after 6 months of treatment. Results. Fluvastatin treatment did not affect HDL-cholesterol or apolipoprotein (apo) AI but resulted in significant decreases in total cholesterol, triglycerides, low-density lipoprotein-cholesterol, apo B and apo E, as well as total serum Lp-PLA(2) activity. In contrast, PON1 activity significantly increased. None of these changes was influenced by Q192R or L55M PON1 polymorphisms. Overall, HDL-Lp-PLA(2) did not change but L55M polymorphism significantly influenced its response to fluvastatin. Specifically, LL homozygotes experienced a significant increase, while M carriers (LM or MM) experienced a non-significant decrease in HDL-Lp-PLA(2) activity (p = 0.030 between groups). Conclusions. Q192R and L55M PON1 polymorphisms did not affect the response of lipids, PON1 and total serum Lp-PLA(2) to treatment with a statin. However, L55M PON1 polymorphism significantly modulated the response of HDL-Lp-PLA(2). It should be noted that this is an association study and therefore provides no proof but only indication that PON1 may also exert Lp-PLA(2) activity in HDL. (C) 2007 IMSS. Published by Elsevier Inc.
Institution and School/Department of submitter: Πανεπιστήμιο Ιωαννίνων. Σχολή Θετικών Επιστημών. Τμήμα Χημείας
Keywords: paraoxonase,polymorphism,lipoprotein-associated phospholipase a(2),platelet-activating factor acetylhydrolase,fluvastatin,lipids,platelet-activating-factor,coronary-heart-disease,c-reactive protein,middle-aged men,density-lipoprotein,serum paraoxonase,factor-acetylhydrolase,phospholipase a(2),plasma-lipoproteins,cardiovascular-disease
URI: http://olympias.lib.uoi.gr/jspui/handle/123456789/10529
ISSN: 0188-4409
Link: <Go to ISI>://000245930700007
http://ac.els-cdn.com/S0188440907000367/1-s2.0-S0188440907000367-main.pdf?_tid=4349964eba4f4306b5f088bc6b5046ce&acdnat=1333110993_a2c1a859da84b1283703dcaedc9276ef
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