PON1 gene polymorphisms and plasma PON1 activities in Takayasu's arteritis disease

Abstract

Background: Takayasu's arteritis (TA) is a chronic inflammation that affects the large vessels; however, its etiology is still unknown. Human serum paraoxonase hydrolyzes oxidized lipids into low-density lipoproteins and could therefore be associated with the prevalence of inflammation processes. Therefore, the purpose of study was to elucidate the influence of PON1 gene polymorphisms and plasma PON1 activities in Takayasu's arteritis disease.

Methods: Fifty-four patients with TA and 173 clinically healthy Mexicans were studied. The PON1 polymorphism was determined by the TaqMan PCR method. PON1 activity was assessed spectrophotometrically by paraoxon (p-nitrophenylphosphate) hydrolysis.

Results: In TA patients, the frequency of PON1(192R) allele (51% vs. 39%, P=0.043, OR=1.60, 95% CI=1.03-2.47), PON1(55M) allele (21% vs. 6.6%, P=0.0001, OR=3.80, 95% CI=2.03-7.10), and PON1(-108T) (60.1% vs. 46%, P=0.011, OR 1.79 (95% CI=1.15-2.79) were significantly higher than in healthy controls. PON1 activity was significantly lower for PON in TA vs. controls (136.14 vs. 322.79 μmol min(-1) ml(-1), P=0.001, showing a decreasing activity in all genotypes in TA patients with respect to the control subjects.

Conclusions: These results show significantly lower PON1 activity associated with HDL-C in TA patients, this activity could be depending on PON1 genotypes; showing that QR/LM/CT has the lowest hydrolytic activity toward paraoxon meanwhile, PON1(192,55,-108) genetic variations are related with reduced PON1 activities, these could be factors contributing to the development of TA disease.