Effect of paraoxonase 1 polymorphisms on the response of lipids and lipoprotein-associated enzymes to treatment with fluvastatin.
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.
Christidis
Dimitrios S
DS
Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece.
Liberopoulos
Evangelos N
EN
Kakafika
Anna I
AI
Miltiadous
George A
GA
Liamis
George L
GL
Kakaidi
Barbara
B
Tselepis
Alexandros D
AD
Cariolou
Marios A
MA
Elisaf
Moses S
MS
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood*; D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D043303:Aryldialkylphosphatase / Q000235:genetics*; D005229:Fatty Acids, Monounsaturated / Q000627:therapeutic use*; D005260:Female; D000077340:Fluvastatin; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy*; D007211:Indoles / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood; D008075:Lipoproteins, HDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic
D000924:Anticholesteremic Agents; D005229:Fatty Acids, Monounsaturated; D007211:Indoles; D008055:Lipids; D008075:Lipoproteins, HDL; D000077340:Fluvastatin; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D043303:Aryldialkylphosphatase