Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an enzyme in the family of proprotein convertases implicated in lipid metabolism and is a significant genetic factor in cardiovascular diseases among various populations. Objective: This study explored the correlation between E670G (rs505151) of the PCSK9 gene and its expression levels with coronary artery disease (CAD) risk in Egyptian patients with type 2 diabetes mellitus (T2DM). Methods: A case-control study was performed on 112 lean subjects compared to 100 T2DM patients without CAD and 84 T2DM patients with CAD to investigate the relationship between PCSK9 expression levels, E670G (rs505151) gene variant, lipid concentrations, and CAD risk in an Egyptian diabetic population. A restriction fragment length polymorphism-polymerase chain reaction (PCR) was employed to assess gene polymorphism and PCSK9 mRNA expression was calculated by quantitative real-time PCR. Results: The prevalence of the E670G (rs505151) AG genotype in diabetics with CAD was significantly greater than the other two groups. The PCSK9 gene expression levels in diabetics with CAD were significantly greater than the other two groups. G allele carriers (AG+GG) had a higher relative PCSK9 expression than A allele carriers. Conclusions: PCSK9 relative expression levels and the E670G (rs505151) AG genotype are CAD risk factors among Egyptian diabetics and are linked positively to the atherogenic index of plasma.