Does the polymorphism of angiotensin-converting enzyme (ACE) gene predict progression of diabetic nephropathy (DN) to chronic renal failure?

A multicenter study demonstrated a significant efficacy of ACE inhibitor in ameliorating the progressive loss of renal function in DN (NEJM 329:1456,1993). In this regard, our recent study on the human genome indicated that the deletion polymorphism (D) on the intron 16 of the ACE gene is a significant prognostic indicator for the progression of IgA nephropathy to chronic renal failure (J Am Sol Nephrol 5:846,1994). Thus, this deletion may represent attenuation of a silencer element per se or be physically linked to other functional component(s) of the gene directly responsible for the progression. As DN and IgA nephropathy share common features, i.e., both often progress to renal failure slowly and insidiously along with development of glomerular sclerosis, we have tested the possibility that the deletion allele may also predict the progression of DN to renal failure. Thirty six patients with NIDDM on chronic dialysis were recruited to this study (Group 1). These patients have diabetic retinopathy and history of diabetes over 10 years. For comparison, another group of 37 NIDDM patients having stable renal function were examined in a similar fashion (Group 2). These 2 groups were comparable in age (61 ± 1 vs. 62 ± 2 yr.), length of history of diabetes (20.3 ± 1.2 vs. 20.4 ± 1.1 yr.), and blood pressure (148 ± 3/78 ± 1 vs. 147 ± 3/81 ± 2 mmHg). Forty seven individuals without history of proteinuria served as controls (Group 3). The DD genotype was found in 11% of controls (Group 3), a value similar to that (10%) reported for the general Japanese population. In the NIDDM patients with stable renal function (Group 2), DD was 16%. In contrast, DD was found in 42% of NIDDM patients with renal failure (Group 1), i.e., significantly more frequently than the other groups. These results indicate that the deletion genotype in the ACE gene is a significant risk factor for chronic renal failure in NIDDM.