Systematic review finds PCSK9, CETP and CDKN2B-AS1 polymorphisms among the strongest genetic contributors to myocardial infarction in Saudi Arabia (J Saudi Heart Assoc 2025)

Introduction: Myocardial infarction (MI) is one of the leading causes of mortality in Saudi Arabia, with individuals sharing genetic, lifestyle, and environmental risk factors. The present investigation aimed to review the literature on genetic susceptibility to MI among Saudi individuals, with a specific emphasis on genome-wide association studies (GWAS) for coronary artery disease (CAD) and MI. Studies have revealed the relationship between polymorphisms in genes such as proprotein convertase subtilisin/kexin type 9 (PCSK9), cholesteryl ester transfer protein (CETP), and cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1), which are involved in lipid metabolism, inflammation, and endothelial function.

Methods: This PROSPERO-registered systematic review and meta-analysis (CRD42024603752) evaluates genetic determinants of myocardial infarction among Saudi adults. Five databases were searched (1989-Oct 2024) according to PRISMA guidelines. Case-control and cohort studies that met the inclusion criteria were analyzed using random-effects models.

Results: Findings suggest that several polymorphic genes are highly associated with MI in Saudi citizens. There is strong evidence indicating that PCSK9, CETP, and CDKN2B-AS1 contribute to susceptibility to MI, though the effect of these polymorphic genes varies. The meta-analysis confirmed that MI is a polygenic disease, and genetic predisposition, in combination with individual lifestyle factors, determines disease progression.

Conclusions: This study establishes that genetic factors significantly contribute to MI in Saudi Arabia. Integrating genetic screening with traditional cardiovascular risk assessments can enhance early intervention strategies. The findings highlight the need for MI prevention programs tailored to specific genotypes in the Saudi population.