Paraoxonase (PON1) 55 Polymorphism and Association with Systemic Lupus Erythematosus

Abstract

Paraoxonase-1 (PON1) is a serum HDL-bound enzyme that hydrolyzes a number of aromatic carboxylic acid esters including lipid peroxides, preventing LDL oxidation. Systemic lupus erythematosus (SLE) patients are at greater risk of oxidative stress, which is associated with abnormal plasma lipid metabolism. In this study, association of PON-55 polymorphism with serum arylesterase (ARE) activities, malondialdehyde (MDA), neopterin, lipids and lipoproteins levels in SLE patients and the development of hypertension was investigated. The present case-control study consisted of 109 SLE patients with and without high blood pressure (BP) and 103 healthy controls from the population in the west of Iran. PON-55 Met<Leu polymorphism was detected by restriction fragment length polymorphism (PCR-RFLP), serum ARE activity, MDA, neoptrin, lipid and apolipoprotein levels were determined by spectrophotometery and HPLC and enzyme assay, respectively. The presence of PON-55 M/M genotype was found to be associated with SLE and the development of high BP. The SLE patients with PON-M (M/L+M/M) allele had significantly lower serum ARE activity, but higher neoptrin and LDL-C than the carriers of corresponding genotypes in control group. The ARE activity was positively correlated with HDL-C and negatively correlated with LDL-C and MDA levels in SLE patients. Whereas, in SLE patients with high BP, ARE activity was only found to be negatively correlated with MDA concentration. These data suggest that PON-55 M/M genotype is a risk factor for SLE. The carriers of this allele have high levels of MDA, neopterin and LDL-C, thus, they are more likely to develop hypertension.

Keywords

• Arylesterase activity
• Blood pressure
• Lipid profile
• Malondialdehyde
• Paraoxonase 55genotype
• Systemic lupus erythematosus