The Regulatory Variant -108C/T in the Promoter of Paraoxonase 1 (PON1) Gene has a More Important Role in Regulating PON1 Activity Compared to rs3735590 in 3ʹ-UTR in Patients with Coronary Artery Disease

Abstract

Background: This study aimed to assess the serum activity of paraoxonase 1 (PON1) in patients with coronary artery disease (CAD) based on two genetic variants including the -108C/T variant in the promoter region and the rs3735590 variant in the binding site of miR-616 at the 3ʹ-UTR of the PON1 gene. Materials and Methods: A total of 140 subjects who exhibited clinical symptoms of CAD underwent diagnostic coronary angiography. The patients with CAD were further categorized into two groups: single-vessel disease (SVD) and multi-vessel disease (MVD). The study variants were genotyped using the restriction fragment length polymorphism (RFLP) technique after polymerase chain reaction amplification. Results: After adjusting for age, gender, body mass index, metformin, and statin usage, a significant association was observed between the -108C/T variant and PON1 activity (P < 0.001). In the sub-groups of both SVD and MVD, individuals with the TC+CC genotypes exhibited significantly higher PON1 activity compared to TT homozygotes (P = 0.001 for SVD and P = 0.01 for MVD). As for the rs3735590 variant, individuals with the A allele (GA+AA genotypes) had higher PON1 activity compared to those with the GG genotype in both the SVD and MVD groups, although the results did not reach statistical significance. Conclusions: Our study findings indicate a significant decrease in PON1 activity among patients with obstructive CAD. Notably, our results suggest that the -108C/T variant exerts a greater influence on PON1 activity compared to the rs3735590 variant. These findings highlight the crucial role of the -108C/T variant in modulating PON1 activity within the context of atherosclerosis.

Keywords

• coronary artery disease
• pon1
• single-nucleotide variation