The DD genotype of the ACE gene polymorphism is associated with progression of diabetic nephropathy to end stage renal failure in IDDM

Background: The insertion-deletion (I/D) polymorphism of the angiotensin converting enzyme gene is a diallelic polymorphism that constitutes a genetic influence on the progression of renal diseases such as IgA nephropathy. Patients with the DD genotype have an accelerated progression towards end stage renal failure in these diseases. The role of the I/D polymorphism in the pathogenesis of diabetic nephropathy in IDDM is unresolved. Patients and methods: We therefore set out to study the contribution of the I/D polymorphism in 79 patients (age 39.5 +/- 7.6 years (mean +/- SD) with end stage renal failure due to diabetic nephropathy, who were recipients of a combined kidney-pancreas transplantation (n = 60), or who were on the waiting list for such a procedure (n = 19). The control series consisted of 82 patients (age 39.5 +/- 9.6 years) without microalbuminuria after fifteen years of IDDM. Results: The ACE genotype distribution in patients was not in accordance with the Hardy-Weinberg equilibrium due to a significant overrepresentation of the DD genotype (X-2 = 8.9, p = 0.01). This resulted in a significant increase of the D-allele frequency in the cases compared to controls (X-2 = 4.9, p = 0.03). The presence of one D-allele did not increase the risk of end stage renal failure (odds ratio ID/II = 1.0, 95% Cl 0.4 - 2.2). The presence of the DD genotype increased the risk of end stage renal failure twofold compared to the other genotypes (odds ratio 2.1, 95% Cl 1.1 - 4.0). The risk estimate seemed slightly higher in patients with good metabolic control (odds ratio 2.6, 95% Cl 1.0 - 7.1), than in patients with poor control (odds ratio 1.6, 95% Cl 0.59 - 4.3). Conclusion: It is concluded that the risk of end-stage renal failure in patients with IDDM is twofold increased in patients with the DD genotype as compared to patients with other genotypes.