Identification of Prognostic Value of Rs3735590 Polymorphism in 3’-Untranslated Region (3’-UTR) of Paraoxonase 1 (PON-1) in Chronic Obstructive Pulmonary Disease Patients who Received Coronary Artery Bypass Grafting (CABG)

Abstract

Background/Aims: In the treatment of serious and symptomatic coronary heart disease (CHD), coronary artery bypass grafting (CABG) is a frequently utilized intervention. In addition, the risk of CHD is strongly associated with the low activity of paraoxonase-1 (PON1), whose 3’-UTR harbors an rs3735590 polymorphism. The aim of this study was to investigate whether the rs3735590 polymorphism could be used as a prognosis marker in chronic obstructive pulmonary disease (COPD) patients undergoing CABG. In addition, the hypothesis, i.e., the rs3735590 polymorphism may be involved in the regulation of PON1 gene expression via modulating its interaction with miRNAs, was tested in this study. Methods: 292 patients diagnosed with COPD and treated with CABG were recruited for this study. Genomic DNA was extracted from clinical samples, and real-time quantitative PCR and Western-blot were used to measure the expression of miR-616 and PON1 in liver cells of different genotypes. Results: 292 COPD patients were divided into three groups according to their genotypes, i.e., rs3735590: CC (212), TC (75), and TT (5), respectively (TC and TT were merged in one group of T carriers for statistical analyses). Patients with the CC genotype were associated with a shorter event-free survival time as compared to patients with the T genotypes. In addition, PON1 was confirmed as a direct target gene of miR-616, while experiments with primary cells of different genotypes showed that miR-616 inhibited the expression of PON1 in CC cells. On the contrary, rs3735590 impaired such inhibitory effect of miR-616 in TT cells. Conclusion: The rs3735590 polymorphism of PON1 acts as a prognostic biomarker in COPD patients treated by CABG.

Paraoxonase 1 and atherosclerosis‐related diseases

“…Higher incidence of the RR phenotype in the patients may be linked with increased atherosclerosis risk. A very recent paper emphasized the significant role of polymorphism in 3′‐untranslated region of PON1's gene to predict coronary artery bypass grafting in patients with COPD …”

“…A very recent paper emphasized the significant role of polymorphism in 3 0 -untranslated region of PON1's gene to predict coronary artery bypass grafting in patients with COPD. 106 Another part of our research regarding PON1 in pulmonary diseases was focused on sarcoidosis. Our results shown significantly decreased PON1 activity in sarcoidosis patients and an inverse association between PON1 activity and a marker of inflammatory response serum amyloid A (SAA).…”

Paraoxonase 1 and Chronic Obstructive Pulmonary Disease: A Meta-Analysis

“…Of the 119 initially identified articles, 100 articles were excluded after screening of titles and abstracts. After screening of full-texts, six studies were excluded because six studies did not focus on PON1 activity of patients with COPD [ 22 , 23 , 24 , 25 , 26 , 27 ]. One study [ 28 ] was excluded because it included the same population as another study [ 29 ].…”