The paraoxonase promoter polymorphism (−107)T>C is not associated with carotid intima-media thickness in Sicilian hypercholesterolemic patients

Abstract

Background and Objectives: 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 (À107)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 (V1 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 (À107)TT genotypes showed lower PON1 activity compared to the RR, LL and CC genotypes. The PON1 (À107)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 (À107)T>C or coding region, Q192R and L55M, polymorphisms and early carotid atherosclerosis in Sicilian hypercholesterolemic subjects.

The Past and Present of Paraoxonase Enzyme: Its Role in the Cardiovascular System and Some Diseases

“…It was noted that the Q192R polymorphism of PON1 was not related to carotid intima thickness (127). A similar result was reported for Sicilian hypercholesterolemic patients in whom early carotid atherosclerosis and polymorphism were found unrelated (128). These results were confirmed by the findings of the EPIC Norfolk study group who did not find any correlation between the cardiovascular system and Q192R variants (129).…”

“…For instance, while the 55M allele was found to be in high frequency in the Portuguese (130), Germans (125) and Taiwanese (122), the L variant was found more common in Italians (120,127) and Brazilians (131). Despite all these findings, Campo et al (128) reported that there was no correlation between the L55M polymorphism and the cardiovascular system. Studies conducted on the Turkish population demonstrat ed that there might be a relation between PON1, Q192R gene polymorphism and coronary artery diseases (132 ).…”

Indications that paraoxonase-1 contributes to plasma high density lipoprotein levels in familial hypercholesterolemia

“…Similar to HDL-C, the contribution of paraoxonase to IMT is debatable. Some studies have reported a significant association between PON1 and IMT in FH patients (9), in middle-aged women (34), and in a subgroup of nonsmokers (35), but there are also a number of reports, including the current one, that did not find an association between PON1 and IMT (30,(36)(37)(38). These differences in outcome suggest that there is only a weak relation between PON1 and IMT that will not be observed in many small studies that lack the power to detect weak effects.…”

“…Remarkably, several studies, including ours, did not observe a significant relation between HDL-C and CCA-IMT (30)(31)(32)(33). Apparently, HDL-C has only minor effects on CCA-IMT.…”

Association between paraoxonase 1 (PON1) enzyme activity, PON1 C(−107)T polymorphism, nutritional status, and lipid profile in children

“…In addition, lower serum PON1 lactonase and arylesterase activities are associated to metabolic alterations related to childhood overweight and onset and/ or development of diabetes and CVD later in life [1,5]. Nevertheless, data on the relationship between PON1 and nutritional status as well as lipid profile in childhood are limited and sometimes controversial, mainly due to differences in measurement techniques and data analysis [13,14]. Such situation is expected to be clarified by the analysis of the interaction between gene, PON1 arylesterase activity, and nutritional status.…”