BackgroundType 2 diabetes mellitus (T2DM) is a worldwide health problem. Prolonged elevated glucose level might cause serious cardiovascular complications. MicroRNA-499 (miRNA-499) is a muscle-specific miRNA expressed highly in normal hearts. The relation of miRNA-499 rs3746444 A>G genotype variants with T2DM and its cardiovascular complication is still vague. ObjectiveThis study aimed to explore the association between miRNA-499 rs3746444 A>G genotype variants with T2DM and its CHD complication in Egyptian population. Subjects and methodsThe study was performed on 180 individuals recruited from Kasr Al-Ainy Hospital. They were sectioned into three groups: 60 T2DM patients without any complication, 60 T2DM patients with CHD and 60 healthy controls. Fasting blood glucose, HbA1c and lipid profile were assessed. MicroRNA-499 gene polymorphism was performed by TaqMan SNP Genotyping assay. ResultsSubjects carrying miRNA-499 GG genotype had a higher risk for T2DM in the codominant and dominant models, with OR (95 % CI) of 10.6 (1.28–88.38) and 10.4 (1.28–85.1), respectively. Subjects carrying GG genotype had a significant risk for CHD in the codominant and dominant models, with OR (95 % CI) of 21.3 (2.69–167.97) and 25.3 (3.25–196.9), respectively. A allele was associated with decreased risk of T2DM and its CHD complication. The frequencies of G allele in T2DM and T2DM with CHD were almost doubled than in control group. ConclusionmiRNA-499 AA genotype and A allele are protective against both T2DM and CHD complication in Egyptian population. GG genotype and G allele are associated with higher risks of T2DM and CHD complication.