Neutrophil-lymphocyte (NLR), platelet-lymphocyte (PLR), eosinophil-lymphocyte (ELR), and monocyte-lymphocyte (MLR) ratios are systemic inflammatory markers related to myocardial infarction. The aim of this study is to investigate the association of Src homology 2-B adapter protein 3 (SH2B3) C784 T and methylenetetrahydrofolate reductase (MTHFR) C677 T polymorphisms (SNP) with systemic inflammatory markers and the severity of coronary artery disease (CAD) in 150 ST-elevation myocardial infarction (STEMI) patients. Single nucleotide polymorphisms were genotyped using the tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) method. The inflammatory markers were calculated. An interventional cardiologist blinded to other data assessed the SYNTAX (SX) Score. Eosinophil and platelet counts were significantly higher in SH2B3 variants than in the wild type. Additionally, SH2B3 variants had significantly higher ELR than the wild type (.12 ± .19 vs .25 ± .34, p = .018). NLR, PLR, ELR, and MLR were considerably higher in MTHFR variants than in the wild type ( p < .05). The SX score was significantly higher in both SH2B3 C784 T (21.24 ± 8.90 vs 15.29 ± 9.40, p = .00) and MTHFR C677 T (20.34 ± 10.21 vs 16.08 ± 8.39, p = .00) variants when compared with wild type. In conclusion, these polymorphisms are associated with several markers of systemic inflammation as well as the severity of CAD.