The Rs3024839 and Rs2227483 Polymorphisms With Immune Pathomechanism Offers a Starting Point for Diagnosis and Susceptibility Testing of Myocardial Infarction Publisher Pubmed



Khosravi Nezhad Z ; Dehghani F ; Molavizade S ; Khanifar H ; Ashrafi M ; Azhdari M ; Faghih Abbasi M ; Baratvand G ; Naeimi S ; Khashei Varnamkhasti K ; Naeimi R ; Khashei Varnamkhasti S ; Hemati E
Source: Scientific Reports Published:2026

Abstract

Long-term primary prevention of myocardial infarction faces challenges, but genetic risk assessment may change this dynamic. We sought for genetic risk loci influencing myocardial infarction and underlying pathomechanisms. AS-PCR used for mutation detection (STAT4_ rs3024839 and IL22_ rs2227483) and confirmed positives by sequencing and Digital PCR. STAT4 and IL22 mRNA levels and chromatin accessibility at SNP sites were evaluated. We assessed SNPs for association with myocardial underlying comorbidities as well as their predictive performance ability. The population flow-sorted CD4+ FOXP3+ Tregs and the level of Foxp3 mRNA were measured and TGF-β1 quantified using ELISA and intracellular staining assay. Immunophenotyping used to identify p53 expression, pro-inflammatory monocytes and circulating endothelial cells. More than 99% samples were positive for mutations. Significant differences in the mutated allele and genotype frequencies were identified at a p value cutoff of 0.05. Analyses identified SNPs as risk factors for comorbid factors with the ability in distinguishing high and low-risk individuals (AUC > 0.9). Differentially accessible chromatin regions influencing STAT4 and IL22 expression were found in risk loci. Lower circulating CD4+ FOXP3+Tregs, Foxp3 expression decline, decreasing TGF-β1 level, increased p53 level, inflammatory state and endothelial dysfunction were further validated. Discovered genotypes open novel opportunities for MI prediction. © The Author(s) 2026.