ACE gene polymorphism and progression of diabetic nephropathy in Korean type 2 diabetic patients: Effect of ACE gene DD on the progression of diabetic nephropathy

Background: Pathophysiological causes of the development and progression of diabetic nephropathy are not well known, but the angiotensin-converting enzyme (ACE) gene polymorphism has been proposed to be involved in its development and progression. Methods: The impact of insertion/deletion (I/D) genotypes on the progression of diabetic nephropathy in 239 Korean patients with type 2 diabetes (99 patients with stable renal function, group 1; 140 patients with declining renal function, group 2) was investigated by retrospective review of clinical data. Results: The frequency of the DD genotype was significantly greater in group 2 compared with group I (30.7% versus 9.1%; P < 0.05). There were no significant differences in age, blood pressure, hemoglobin A_1c levels, or lipid profiles among ACE genotype groups. However, the prevalence of retinopathy was significantly greater in patients with the DD genotype (DD, ID, and II, 90.4%, 71.2%, and 70.6%, respectively; P < 0.05). Patients with the DD genotype reached the end point (serum creatinine > 2.0 mg/dL [176.8/μmol/L]) faster than those with the other genotypes (DD, 11.38 ± 4.08 years; ID, 13.85 ± 4.04 years; II, 14.04 ± 4.06 years, respectively; P < 0.05) and took significantly less time to reach dialysis therapy (DD, 13.10 ± 4.45 years; ID, 16.21 ± 4.74 years; II, 15.13 ± 4.09 years, respectively; P < 0.05). In multiple logistic regression analysis, systolic blood pressure and DD genotype showed significant correlations with the progression of diabetic nephropathy. In patients with the DD genotype, the odds ratio was 3.881 (95% confidence interval, 1.564 ∼ 9.628; P = 0.003) compared with those with the II genotype. Conclusion: It is suggested that the ACE gene DD genotype might be a significant risk factor for the progression of diabetic nephropathy.