Influence of PON1 gene variants and enzymatic activity on the risk of coronary artery disease: a meta-analysis of case-control studies Sana Ashiq 1 , Kanwal Ashiq 2 1 Centre for Applied Molecular Biology, University of the Punjab, Pakistan, 2 Faculty of Pharmaceutical Chemistry, Superior University, Pakistan Background: Non-communicable diseases (NCDs), including coronary artery disease (CAD), is responsible for high mortality and morbidity rate in developed or developing countries. It is a multifactorial disease that involves a complex relationship between either gene-environment or gene-gene. The paraoxonase 1 ( PON1 ) gene encodes a paraoxonase enzyme that plays an essential role in atherosclerosis due to its antioxidative properties. Several studies have been conducted to understand single nucleotide polymorphisms (SNPs) in this gene and CAD. However, the findings were not consistent and remain unclear. Therefore, this meta-analysis study was designed to analyze the available literature from different cohorts that may provide us with more conclusive findings. Objective: To understand the relationship between PON1 gene polymorphisms (rs662 and rs854560) in coronary artery disease. Methods: This study was conducted according to PRISMA guidelines.The relevant literature was searched using various keywords through various electronic databases. The pooled odd ratios (ORs) were used to evaluate the role of variants in the PON1 gene and CAD. Data analysis was performed by the MetaGenyo program. Results: Final analysis was performed on the ten eligible studies. In the coding region, SNPrs662 significantly increased the risk of CAD (OR 1.16, CI 1.00–1.33). However, the results were non-significant for the second polymorphism rs854560. Further, compared to healthy subjects, PON1 enzyme levels were much lower in CAD patients. Conclusions: Our pooled analysis suggested a significant association between rs622 and CAD compared to rs854560. However, in the future, there is a need to conduct large sample-size genetic association studies, which can provide us better understanding of the association or effect of these variants with the risk of coronary artery disease. Keywords: CAD; Meta-analysis; PON1; Polymorphisms Study Registration: PROSPERO registration number CRD42020202278 References 1. Ashiq S, Ashiq K. The role of paraoxonase 1 (PON1) gene polymorphisms in coronary artery disease: a systematic review and meta-analysis. Biochemical Genetics. 2021 Aug;59:919-39. 2. Ashiq S, Ashiq K, Shabana SU, Qayyum M, Sadia H. Prevalence and role of different risk factors with emphasis on genetics in development of pathophysiology of coronary artery disease (CAD). Pakistan Heart Journal. 2019;52(4). 3. Ashiq S, Ashiq K. In-silico analysis of PON1, PON2 and PON3 genes role in coronary artery disease. International Journal of Computational Biology and Drug Design. 2020;13(4):415-23.
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