Genomic variants and epidemiology of atherosclerosis – worldwide correlation analysis and utilization of atherosclerosis gene variants for identification of drug target candidates with bioinformatics approach

Introduction: Atherosclerosis (AS) is a major risk factor for cardiovascular disease (CVD), which is the leading cause of death worldwide. Genetic factors are an integral factor in the cause of AS. This study aims to correlate epidemiological data, prevalence and mortality of AS worldwide with Single Nucleotide Polymorphisms (SNPs) associated with susceptibility and severity in different populations. Hence, utilized the gene variants to discover potential drug targets using bioinformatics. Material and methods: This study used a secondary data-driven bioinformatics approach to analyze the correlation between genetic variants associated with AS and epidemiological data from different regions of the world. Genetic data were obtained from the GWAS Catalog, while epidemiological data were collected from WHO and Our World in Data. The analysis was performed by fi ltering SNPs based on several criteria, namely the missense variant category, signifi cant p-value < 10-5, and prediction of variant impact using PolyPhen (Possibly Damaging) and SIFT (Deleterious). The correlation between allele frequency and AS prevalence and mortality was analyzed using the Pearson test. Results: The results of the study obtained three missense variants rs11466653 in TLR10 , rs2296172 in MACF1 and rs6025 in F5 . at rs11466653 has a role in the pathogenesis of AS with analysis using SNPnexus which shows the possibility of damaging (PolyPhen) and deleterious (SIFT) properties in addition to the results of the correlation test signifi cant to the prevalence and mortality of global AS (p < 0.05). Due to the challenge of drugging all potential target genes, our study was only able to identify the F5 gene as a viable target. The results of the identifi cation of candidate drugs targeting the F5 gene indicate that copper has the potential to be used in the treatment of AS. This assessment is based on a scoring analysis where the drug obtained a score of 6 indicating excellent quality or suitability in the context of drug repurposing for AS treatment. Conclusion: The fi ndings in this study will encourage efforts to improve AS diagnosis and early treatment, as well as increase public awareness of the importance of genetic factors and lifestyle in preventing this disease. This study can also be a reference for further research focusing on genetic intervention and development of personalized therapy for AS. Therefore it can provide broader benefi ts for global public health.