ORIGINAL RESEARCH article
Front. Endocrinol.
Sec. Cardiovascular Endocrinology
Volume 16 - 2025 | doi: 10.3389/fendo.2025.1688319
Association of Paraoxonase-1 (p.L55M) and Paraoxonase-2 (p.S311C) polymorphisms with coronary artery disease in North Indian Punjabi population
Provisionally accepted
- 1Georgetown University Medical Center, Washington, United States
- 2Government Medical College Amritsar, Amritsar, India
- 3Dr Radhakrishnan Government Medical College, Hamirpur, India
- 4National Eye Institute (NIH), Bethesda, United States
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Background: 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. Methods and Results: 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). Conclusions: Our results indicate a significant and independent association of PON2 (p.S311C) polymorphism with CAD even after gender stratification in North Indian Punjabi population.
Keywords: Coronary Artery Disease, PON1, PON2, polymorphisms, haplotype, North India
Received: 19 Aug 2025; Accepted: 23 Sep 2025.
Copyright: © 2025 Bhat, Singh, Lone and Goyal. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Shiwali Goyal, goyal.shiwali@gmail.com
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