Paraoxonase 1 (PON1) 55 polymorphism, lipid profiles and psoriasis

Background Paraoxonase 1 (PON1) is a serum high-density lipoprotein-bound enzyme with antioxidant function. It hydrolyses lipid peroxides, protecting low-density lipoproteins from oxidative modifications. Patients with psoriasis are at greater risk of oxidative stress, which is associated with abnormal plasma lipid metabolism. Objectives In this study, association of the PON1 55 M allele with serum arylesterase (ARE) activity, malondialdehyde (MDA), lipid profiles and psoriasis was investigated. Methods The present casecontrol study consisted of 100 patients with psoriasis with and without cardiovascular diseases (mean age 35.3 years) and 100 sex- and age-matched unrelated healthy controls (mean age 35.7 years) from the population of western Iran. The PON1 55 Met>Leu polymorphism was detected by polymerase chain reactionrestriction fragment length polymorphism. Serum ARE activity, MDA, and lipid and apolipoprotein levels were determined spectrophotometrically, by high-performance liquid chromatography and by enzyme assay, respectively. Results The presence of the PON1 55 M allele was found to be associated with psoriasis (odds ratio = 1.96, P = 0.017). The patients with psoriasis with the PON1 M (M/L + M/M) allele had higher MDA levels (4.12 +/- 0.88 vs. 2.24 +/- 0.55 mu mol L-1, P < 0.001), apolipoprotein B (APOB)/APOA1 ratio (0.91 +/- 0.66 vs. 0.66 +/- 0.35, P = 0.004), APOB (111 +/- 38.7 vs. 88.3 +/- 22.5 mg mL(-1), P = 0.001) and lipoprotein(a) [LP(a)] (21.9 +/- 18.4 vs. 15.8 +/- 16.6 mg mL(-1), P = 0.034), but lower ARE activity (39.6 +/- 11 vs. 45.9 +/- 11.8 U mL(-1), P = 0.031) than the control subjects. ARE activity showed a significant positive correlation with APOA1 and a negative correlation with MDA concentration in patients with psoriasis. Conclusions The PON1 55 M allele is a risk factor for psoriasis. Carriers of this allele have high levels of MDA, APOB and LP(a), a high APOB/APOA1 ratio and low ARE activity. These results indicate that oxidative stress, impairment of the antioxidant system and abnormal lipid metabolism may play a role in the pathogenesis and progression of psoriasis and its related complications. These data suggest that patients with psoriasis are more susceptible to vascular diseases.