# Association of Paraoxonase-1 (p.L55M) and Paraoxonase-2 (p.S311C) polymorphisms with coronary artery disease in North Indian Punjabi population

## TL;DR

This study finds that specific genetic variations in PON2 are linked to a higher risk of coronary artery disease in the North Indian Punjabi population.

## Contribution

The study identifies a novel association between PON2 (p.S311C) polymorphism and CAD in a specific ethnic population.

## Key findings

- PON2 (p.S311C) SC and CC genotypes increase CAD risk by 2- and 3.5-fold in North Indian Punjabi individuals.
- The LC haplotype of PON1 and PON2 is independently associated with a 2.34-fold increased CAD risk.
- Multiple inheritance models confirm the PON2 (p.S311C) polymorphism's role in CAD susceptibility.

## Abstract

Paraoxonases (PONs) are a unique family of calcium-dependent enzymes which are tightly associated with the high-density lipoprotein cholesterol (HDL-C), plays a crucial role in protecting the low-density lipoprotein cholesterol (LDL-C) from oxidation, thereby providing protection against atherosclerosis-a key factor for the pathogenesis of coronary artery disease (CAD). The activity of PON enzymes is influenced by genetic polymorphisms in the PON genes. The present case-control study was performed to investigate the association of PON1 (p.L55M, rs854560) and PON2 (p.S311C, rs7493) polymorphisms with CAD in the North Indian Punjabi population.

The present study included 211 CAD patients and 260 healthy controls genotyped using the polymerase chain reaction-reaction fragment length polymorphism (PCR-RFLP) technique. Binary logistic regression analysis revealed that the SC and CC genotypes of the PON2 (p.S311C) conferred 2-and 3.5-folds increased risk for CAD (OR: 2.03, 95%CI: 1.36-3.01, p=0.001; OR: 3.49, 95%CI: 1.86-6.55, p=0.001, respectively). Moreover, the dominant (OR: 2.29, 95%CI: 1.58-3.32, p=0.0001), co-dominant (OR: 1.62, 95%CI: 1.11-2.36, p=0.012), recessive (OR: 2.58, 95%CI: 1.41-4.72, p=0.001), and log-additive (OR: 1.92, 95%CI: 1.46-2.54, p=0.0001) are the best-fit inheritance models to predict the susceptible gene effects. Furthermore, the LC haplotype (PON1 and PON2) was found to be significantly and independently associated with the increased risk of CAD (OR: 2.34, 95%CI: 1.65-3.32, p=0.0001).

Our results indicate a significant and independent association of PON2 (p.S311C) polymorphism with CAD even after gender stratification in North Indian Punjabi population.