Paraoxonase 1 activity and genotyping in systemic lupus erythematosus and their relationships with cardiovascular complications
Introduction: Systemic lupus erythematosus (SLE) is characterized by an enhanced risk of atherosclerosis and cardiovascular diseases (CVD). Human serum paraoxonase 1 (PON1), an antioxidant enzyme closely associated with high density lipoprotein (HDL), has been implicated in the prevention of low density lipoprotein (LDL) oxidation, and these may provide HDL-associated protection against atherosclerosis. The Aim: Our objective was to evaluate PON1 activity and genotypes in SLE patients and their relationships to cardiovascular complications and some other risk factors of cardiovascular diseases in those patients. Patient and Methods: Thirty SLE patients, subdivided into patients with CVD and without CVD, and fifteen matched healthy control subjects were studied. Laboratory investigations included lipid profile, lupus anticoagulants (LA), anticardiolipin antibodies (aCL). PON1 activity was determined by paraoxon substrate. PON1 genotyping was conducted by PCR amplification, followed by polymorphism-specific restriction enzyme digestion and gel electrophoresis. Results: Our study revealed that PON1 activity was significantly decreased in SLE patients groups compared to controls and in SLE patients with CVD compared to those without CVD (p<0.001). PON1 activity was significantly negatively correlated with total cholesterol, LDL-C and LDL-C/HDL-C ratio, positively correlated with HDL-C but not significantly correlated with triglycerides, disease activity, LA or aCL antibodies. As regard PON1 192 gene polymorphism, there was significant increase in B allele frequency in SLE patients with CVD compared to those without CVD and control groups, while no significant difference was found between SLE patients without CVD and control group. As regard PON1 55 gene polymorphism, there was no significant difference in genotype distribution or allele frequency between the three groups. The Odds ratio of development of CVD in SLE patients who carry PON1 192B allele was 6 (95% CI 1.2-30.7, p<0.05). PON1 activity determined by paraoxon substrate was significantly higher in BB and LL, intermediates in AB and LM, and lower in AA and MM genotypes. Conclusion: The decreased PON1 activity and the increased PON1 192B allele frequencies in SLE patients may have a role in development of cardiovascular complications. Further studies on large number of patients of PON1 gene polymorphisms of are needed to elucidate this relationship.
Keywords:Systemic lupus erythematosus, cardiovascular disease, paraoxonase enzyme, paraoxonase genotypes.
Egyptian Journal of Medical Human Genetics Vol. 9 (2) 2008: pp. 201-214