Paraoxonase genotype, LDL-oxidation and carotid atherosclerosis in male life-long smokers.
Paraoxonase (PON-1) is a high-density lipoprotein (HDL) associated enzyme that hydrolyzes lipid peroxides in vitro, which may therefore protect against the onset of atherosclerosis. Heavy smokers are more exposed to oxidative stress and hence at high-risk for oxidative modification of LDL. Our hypothesis is that the anti-oxidative properties of PON-1 inhibit LDL oxidation, especially in populations exposed to high oxidative stress. We have studied the effects of PON-1 genotype and smoking to variation in oxidative status parameters and intima-media thickness (IMT), a surrogate marker of atherosclerosis. The contribution of two common polymorphisms in the PON-1 gene (Q192R and L55M) to LDL oxidizability, autoantibodies directed against oxLDL and IMT were studied in 207 male life-long smokers. Smokers were classified into average, heavy and excessive smokers based on pack years of cigarettes smoked. PON-1 genotype was not associated with autoantibodies to oxLDL, LDL oxidizability or IMT. Smoking was associated with IMT in subgroups with the high levels of LDL, but not in the population at large. The lack of association of PON-1 genotype with oxidative status parameters and IMT suggests that PON-1 is not a major inhibitor of LDL oxidation in a population of life-long smokers.
Van Himbergen
Thomas
T
Research Laboratory of the Department of Clinical Chemistry, University Medical Centre Utrecht, Utrecht, The Netherlands. t.m.vanhimbergen@lab.azu.nl
Roest
Mark
M
De Waart
Frouwkje
F
De Graaf
Jacqueline
J
Voorbij
Hieronymus
H
Van Tits
Lambertus
L
Stalenhoef
Anton
A
D000367:Age Factors; D043303:Aryldialkylphosphatase / Q000235:genetics* / Q000378:metabolism*; D001323:Autoantibodies / Q000097:blood; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000235:genetics*; D015897:Comorbidity; D005838:Genotype; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D010084:Oxidation-Reduction; D011110:Polymorphism, Genetic; D012907:Smoking / Q000009:adverse effects* / Q000453:epidemiology; D014463:Ultrasonography
D001323:Autoantibodies; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D043303:Aryldialkylphosphatase