Assessing the relationship of paraoxonase-1 Q192R polymorphisms and the severity of lung disease in SM-exposed patients

Abstract

Late respiratory complications in patients suffering from pulmonary lesions due to sulfur mustard (SM) gas are asthma, chronic obstructive pulmonary disease and bronchiectasis. Recently PON1 antioxidant activity draws attention as the enzyme which prevents the oxidation of lipoproteins during oxidative stress. In this study we aimed to investigate PON1 192 polymorphisms and paraoxonase and arylesterase activity in the serum of SM-exposed lung disease patients. Also, we examined the detection of PON1 and apoA1 proteins in BAL fluid. 101 male patients were included who were categorized to three groups of mild, moderate and severe suffering from pulmonary lesions due to SM. Significant reduction in paraoxonase activity [Healthy: 412.46 ± 89.1 U/L, Severe: 89.66 ± 20.7 U/L] (p < 0.0001) and arylesterase activity [Healthy: 25826.4 ± 4425.23 U/L, Severe: 16760.43 ± 3814.9 U/L] (p < 0.0001) with increase in severity of disease was demonstrated statistically. With respect to the distribution of the PON1 polymorphism, the RR genotype was more frequent in severe patients [37.2%] than healthy group [10%] (p < 0.05) and no significant regression was found between genotype and PON1 activity. On the other hand, the results of PON1 and apoA1 detection illustrated that only apoA1 protein was found in BAL fluid. According to our findings it seems that increase in the stress oxidative in chemical injured veterans with pulmonary complications comes with reduction in PON1 enzyme activity and appearance of RR genotype rises up with the increase in disease severity. Since a significant correlation between enzyme activity and genotype was not observed altering these two variables with each other requires more studies.

Suppressed paraoxonase-1 activity associates with elevated oxylipins and the presence of small airways disease in patients with rheumatoid arthritis

“…PON1 is a serum enzyme primarily synthesized in the liver and secreted into the plasma where it associates with HDL. PON1 has multiple functions including the metabolism of pro-inflammatory, oxidized lipids in LDL and HDL, and has been implicated in the pathogenesis of several disorders including diabetes, coronary heart disease (CHD), cancer, and lung disease [ 5 , 27 ]. Our work in the K/BxN mouse model of RA recently showed that over-expression of the human PON1 transgene, which causes a twofold to threefold increase in circulating PON1 activity, reduces RA joint disease activity and associated with lower levels of the pro-inflammatory oxylipins 5-HETE and 15-HETE [ 26 ].…”

“…The role of PON1 in lung disease remains largely unclear, although some studies have suggested a possible protective role in chronic obstructive lung disease, and inflammatory pulmonary disease related to mustard gas exposure [ 27 , 28 ]. The PON1 protein has been identified in non-ciliated bronchiolar epithelial cells (clara cells), which maintain the epithelium of the distal conducting airways of the lungs [ 29 ], and both the arylesterase activity and protein levels of PON1 have been identified in induced sputum from healthy volunteers [ 30 ].…”

Abnormal paraoxonase-1 (PON1) enzyme activity in idiopathic inflammatory myopathies

“…Because the PON1 Q192R polymorphism is a major determinant of the enzyme activity of PON1, and has been associated with both vascular and pulmonary outcomes in the general population [12,26], we examined its association with disease outcomes in IIM patients. Clinical characteristics of IIM patients were first examined between PON1 QQ, QR and RR genotypes (Table 5).…”