The paraoxonase promoter polymorphism (-107)T>C is not associated with carotid intima-media thickness in Sicilian hypercholesterolemic patients.
OBJECTIVE
Increased plasma low-density lipoprotein-cholesterol (LDL-C) levels in hypercholesterolemic subjects are associated with enhanced LDL oxidation that represents an additional risk for atherosclerotic disease. Human serum paraoxonase (PON1), a high-density lipoprotein (HDL) associated enzyme, has been shown to protect LDL from oxidation, thus playing an important role in reducing the risk of atherosclerosis. PON1 gene polymorphisms have been found to be associated with the variations in serum PON1 levels and activities, and with the risk for coronary artery disease (CAD). This study was performed to evaluate the contribution of the PON1 promoter (-107)T>C and the coding region Gln 192 Arg (Q192R) and Leu 55 Met (L55M) polymorphisms to the presence of carotid atherosclerosis in 208 Sicilian subjects with primary hypercholesterolemia.


METHODS
Carotid artery intima-media wall thickness (IMT) was measured as an indicator of early atherosclerotic disease. The subjects were classified according to whether they have a normal (<or=1 mm) or an abnormal (>1 mm) IMT. Subjects were also investigated for physical and biochemical parameters, including PON1 activity.


RESULTS
No significant differences were detected among the PON1 genotypes with respect to age, sex, BMI, plasma lipids, systolic blood pressure in both groups of patients. There were significant differences between PON1 genotypes with respect to PON1 activity. The 192QQ, 55MM and (-107)TT genotypes showed lower PON1 activity compared to the RR, LL and CC genotypes. The PON1 (-107)T>C genotype distribution in both IMT groups showed no significant differences in percentage of TT, CT and CC genotypes. Similar results were obtained analyzing the Q192R and L55M genotype frequencies. Stepwise forward logistic regression analysis confirmed the lack of association between PON1 genotypes and carotid abnormalities.


CONCLUSIONS
In conclusion, our data provided no evidence of a significant association between either PON1 promoter (-107)T>C or coding region, Q192R and L55M, polymorphisms and early carotid atherosclerosis in Sicilian hypercholesterolemic subjects.
Campo
Salvatore
S
Department of Internal Medicine, University of Messina, Messina, Italy.
Sardo
Maria A
MA
Trimarchi
Giuseppe
G
Bonaiuto
Michele
M
Castaldo
Maria
M
Fontana
Luisa
L
Bonaiuto
Antonio
A
Bitto
Alessandra
A
Saitta
Carlo
C
Saitta
Antonino
A
D043303:Aryldialkylphosphatase / Q000097:blood / Q000235:genetics*; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000473:pathology; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging / Q000235:genetics*; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000000981:diagnostic imaging / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016366:Open Reading Frames; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D012802:Sicily; D017539:Tunica Intima / Q000000981:diagnostic imaging / Q000473:pathology; D017540:Tunica Media / Q000000981:diagnostic imaging / Q000473:pathology; D014463:Ultrasonography
D043303:Aryldialkylphosphatase; C468406:PON1 protein, human