Abstract
Inflammatory cytokines are pivotal in the pathophysiology of acute coronary syndrome (ACS) and have been associated with major adverse cardiovascular events. In this study, we aimed to assess the association of eight polymorphisms in IL-10, IL-6, and TNF-α with the risk of ACS through a systematic review, meta-analysis, and trial sequential analysis. A comprehensive literature review was conducted across multiple databases, including PubMed/Medline, Web of Science, Scopus, and Cochrane Library, up until August 8, 2024. The Review Manager 5.3 software was utilized to compute the effect sizes such as the odds ratio accompanied by a 95% confidence interval. Out of 1499 records identified from databases, sources, or electronic searches, 51 articles were included in qualitative and quantitative syntheses (meta-analysis). For IL-6 -174G > C, the allelic and homozygous models showed significant associations with ACS risk. IL-6 -572G > C showed no significant association across all genetic models. IL-10 polymorphisms (-592C > A, -819C > T, and -1082A > G) generally showed no significant associations. TNF-α -308G > A polymorphism showed significant associations in all models. TNF-α -1031T > C and -238G > A showed no significant associations, with varying degrees of heterogeneity. Results suggest that certain cytokine polymorphisms, notably IL-6 -174G > C and TNF-α -308G > A, may play a crucial role in increasing susceptibility to ACS. These associations are especially pronounced in certain ethnic groups, such as Asians and Arabs, highlighting the importance of considering genetic diversity in clinical assessments.