Immunology Letters 152 (2013) 77–82 Contents lists available at SciVerse ScienceDirect Immunology Letters jo u r n al homep age: www.elsevier.com/locate/immlet PON1 gene polymorphisms and plasma PON1 activities in Takayasu’s arteritis disease Claudia Huesca-Gómez a , María Elena Soto b , Vicente Castrejón-Téllez a , Oscar Pérez-Méndez c , Ricardo Gamboa a,∗ a Department of Physiology, Instituto Nacional de Cardiología “Ignacio Chávez”, Juan Badiano No. 1, Col. Sección XVI, C.P. 14080 México, DF, Mexico b Department of Immunology, Instituto Nacional de Cardiología “Ignacio Chávez”, Juan Badiano No. 1, Col. Sección XVI, C.P. 14080 México, DF, Mexico c Department of Molecular Biology, Instituto Nacional de Cardiología “Ignacio Chávez”, Juan Badiano No. 1, Col. Sección XVI, C.P. 14080 México, DF, Mexico a r t i c l e i n f o Article history: Received 1 February 2013 Received in revised form 13 April 2013 Accepted 20 April 2013 Available online xxx Keywords: Takayasu’s arteritis Paraoxonase activity Paraoxonase polymorphisms a b s t r a c t 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 spectropho- tometrically 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 mol 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. © 2013 Elsevier B.V. All rights reserved. 1. Background Takayasu’s arteritis (TA), also known as pulseless disease, is a chronic inflammation that affects the large vessels, predomi- nantly the aorta and its main branches. Vessel inflammation leads to wall thickening, fibrosis, stenosis, and thrombus formation. In the early stages, the arterial damage is not easily detected, but as the disease progresses it produces acute inflammation, endothe- lial dysfunction, damage to the arterial media, and atherosclerotic aortic aneurysm formation [1–3]. TA affects women most commonly in their reproductive age and is more frequent in Japan, South East Asia, India, and Mexico, although it can be found worldwide [1,2,4]. The etiology of the disease is unknown; however, many stud- ies have shown that local inflammation sometimes persists even ∗ Corresponding author. Tel.: +52 55 55 73 29 11x1278; fax: +52 55 55 73 09 26. E-mail addresses: rgamboaa 2000@yahoo.com, rgamboa2000@gmail.com (R. Gamboa). after acute inflammation apparently subsides. Local vasculitis may latently occur without apparent inflammatory manifestations, causing chronic vascular cell damage, which may finally develop lesions with histological features resembling the atherosclerotic aortic aneurysm [3,5]. Several clinical and epidemiological studies have demon- strated that high-density lipoproteins (HDL) protect against the inflammatory process by a mechanism that involves binding and carrying away oxidant molecules. HDL stimulates the synthesis of nitric oxide by the endothelium [6] and assists endothe- lial function through their associated enzyme, paraoxonase-1 (PON1) [7]. This enzyme catalyzes the conversion of the pro- atherogenic low-density lipoprotein (LDL)-lipoperoxides to the corresponding lipohydroxides that are innocuous for the endothe- lium [7]. Recent studies suggest that some individuals may have specific PON1 genotypes that are associated with low PON1 plasma levels or low enzyme activities; the hydrolytic efficiency of PON1 depends on the single nucleotide polymorphisms (SNP) 192 QR [7–9]. Costa et al. [10] reported that adults with the same genotype may have 0165-2478/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.imlet.2013.04.005