ASSOCIATION OF C-REACTIVE PROTEIN, HOMOCYSTEINE, AND MTHFR C677T GENE POLYMORPHISM IN PATIENTS WITH CORONARY ARTERY DISEASE

Abstract

Background & Objective: Coronary artery disease (CAD) remains a leading cause of cardiovascular mortality worldwide, driven by complex gene-environment interactions, systemic inflammation, and metabolic dysregulation. This study aimed to investigate the association between high-sensitivity C-reactive protein (hs-CRP), plasma homocysteine levels, and methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism in patients diagnosed with CAD. Methods: A cross-sectional study was conducted evaluating n = 220 subjects, including CAD patients (n = 140) confirmed via coronary angiography and healthy controls (n = 80). Serum hs-CRP and plasma total homocysteine were measured using high-sensitivity ELISA and chemiluminescent immunoassay, respectively. MTHFR C677T (rs1801133) single nucleotide polymorphism genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Logistic regression and ROC curve analyses evaluated independent cardiovascular risk predictors. Results: Serum hs-CRP (4.82 ± 1.65 vs. 1.35 ± 0.48 mg/L, p < 0.001) and plasma homocysteine (18.65 ± 5.42 vs. 9.82 ± 2.15 µmol/L, p < 0.001) were significantly elevated in CAD patients compared to controls. The MTHFR 677TT homozygous mutant genotype frequency was substantially higher in CAD patients (22.9% vs. 6.25%, p = 0.002). Carrying the TT genotype was strongly associated with severe hyperhomocysteinemia (> 15 µmol/L; OR = 5.12, p < 0.001) and multi-vessel CAD involvement. Multivariable logistic regression confirmed hs-CRP > 3.0 mg/L (aOR = 4.25, p < 0.001), Homocysteine > 15 µmol/L (aOR = 3.82, p < 0.001), and MTHFR 677TT genotype (aOR = 2.95, p = 0.006) as independent predictors of CAD severity. Conclusion: MTHFR C677T polymorphism, elevated homocysteine, and inflammatory hs-CRP demonstrate a synergistic association with coronary artery disease onset and severity. Genetic susceptibility mediated by the MTHFR 677TT genotype exacerbates hyperhomocysteinemia, promoting endothelial dysfunction and systemic vascular inflammation.