Angiotensin converting enzyme insertion/deletion (I/D) (rs4646994) and Vegf polymorphism (+405G/C; rs2010963) in type II diabetic patients: Association with the risk of coronary artery disease

Hypothesis: Little is known about the concomitant presence of the angiotensin-converting enzyme (ACE) (rs4646994) D allele and vascular endothelial growth factor(VEGF) (+405G/C; rs2010963) G allele on the susceptibility of coronary artery disease (CAD). Here we examined the hypothesis that ACE-D and VEGF-G alleles act synergistically to increase the severity of CAD in patients with type II diabetes mellitus (T2DM). Materials and methods: The VEGF (rs2010963) and ACE (rs4646994) genotypes were detected by polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) and PCR, respectively in 510 T2DM patients undergoing their first coronary angiography. Diabetic patients were classified as T2DM patients with and without CAD (control). Results: The crude odds ratio (OR) for the presence of CAD in ID+DD and D allele carriers were 1.98 (p=0.01) and 1.55 (p=0.001), respectively. Also, adjusted ORs in the presence of normolipidemia and the absence of history of hypertension for the risk of CAD in the either ACE(rs4646994) D allele or VGEF(rs2010963)-G alleles were 2.08 (p=0.004) and 1.75 (p=0.024), respectively. In addition, the concomitant presence of the ACE-D and VEGF-G alleles increased the risk of CAD 2.25-fold (p=0.043). Conclusion: Our results indicated that ACE(rs4646994)-D allele alone and in the presence of VEGF(rs2010963)-G allele can be an important independent risk factor for susceptibility of CAD in T2DM patients even after correcting for conventional risk factors in a population of Iran.