Abstract Background Genome-wide association studies have identified novel genes related to coronary artery disease (CAD). These studies have been replicated in distinct ethnic populations, returning inconsistent results. Our work aimed to study the frequency of C and T alleles of GLUL polymorphism genetic variant rs10911021 among Egyptians with coronary artery disease in comparison to apparently healthy subjects. Our study included 420 patients with CAD (180 CAD without T2DM, 240 CAD with T2DM patients) and 200 control subjects. All subjects were genotyped for rs10911021 by real-time polymerase chain reaction. Results For rs10911021, the frequency of (C/T + T/T) genotypes was significantly higher in CAD patients with and without T2DM than in controls (55(45 + 10) % vs. 22(19 + 3) %; p < 0.001) and (50(45 + 5) % vs. 22(19 + 3) %; p < 0.001 respectively). The genotype C/C was the most frequent among the controls (78%). The presence of GLUL polymorphism was associated with 4.4-fold increased risk to develop CAD in diabetic patients (OR = 4.4, 95% CI = (2.2–8.7); p < 0.001) and was associated with 2.3-fold increased risk to develop CAD (OR = 2.3, 95% CI = (1.1–4.6); p = 0.0213). Conclusion In conclusion, among Egyptians, the GLUL polymorphism susceptibility variant rs10911021 is associated with CAD, with and without T2DM.