BACKGROUND: The oxidative stress is regarded as one of the main contributors to the health problem. Cyclooxygenase-2 (COX-2) and matrix metallopeptidase-9 (MMP-9) are two of the important genes that are reported to be involved in the cardiovascular disease (CVD) development in the molecular and genetic association studies. The aim of this study was to evaluate the level of expression of COX-2 and MMP-9 after selenium supplementation in patients with coronary artery disease (CAD).METHODS: In this sub-study of Selenegene study, subjects were randomly divided into groups, 19 subjects who received selenium and 22 patients with CAD who received placebo. Patients received either 200-mg selenium yeast tablets or placebo tablets after a meal, once daily for 60 days. The messenger ribonucleic acid (mRNA) levels of the selenium and prostaglandin-endoperoxide synthase 2 (PTGS2) (COX-2) and MMP-9 genes products were determined before and after the study.RESULTS: In this sub-study, 41 Iranian patients with CVD were enrolled (placebo group: n = 22, selenium intervention: n = 19). Fasting blood sugar (FBS) was higher among placebo group than selenium group (93.4 ± 12.7 vs. 124.4 ± 40.6 mg/dl, P = 0.03). Triglyceride (TG) level was higher among selenium group versus placebo group (123.3 ± 34.0 vs. 184.8 ± 69.4 mg/dl, P = 0.006). The data analysis demonstrated that the expression of MMP-9 and COX-2 genes did not change significantly in both selenium and placebo groups.CONCLUSION: This study showed a positive association between the expression of MMP-9 and COX-2 in the patients with CAD who received selenium but not the placebo groups. Yet, these findings need to be confirmed in further details and expanded sample size.