Angiotensin I converting enzyme gene polymorphism in non-insulin dependent diabetes mellitus

Kidney Int. 1996 Aug;50(2):657-64. doi: 10.1038/ki.1996.362.


A total of 168 patients with non-insulin dependent diabetes (NIDDM) followed over 10 years were recruited in this study. The patients were divided into two groups: Group 1 patients had a stable renal function (N = 96) and Group 2 had a declining renal function (N = 72). Group 1 included those whose serum creatinine was normal five years ago but had increased to > or = 2 mg/dl or those who has reached end-stage renal failure (requiring dialysis) by the time of study. All patients were genotyped for the insertion/deletion (I/D) polymorphism of the ACE gene, the M235T polymorphism of the angiotensinogen (Atg) gene and the A1166C polymorphism of the angiotensin II type 1 receptor (AT1) gene. The genotype frequency distributions of M235T Atg and the A116C AT1 gene polymorphisms were not different between Group 1 versus Group 2. While the frequency of the ACE DD genotype in Group 1 (7.3%) was comparable to that of the general population, the DD frequency was significantly higher in Group 2 (26.4%) than in Group 1 (odds ratio, 4.56; 95% confidence interval, 1.80 approximately 11.56, P < 0.001). Among all 168 patients studied, the renal survival rate was significantly lower among DD than ID (P < 0.005) or II patients (P < 0.001). In patients with a declining renal function (Group 2), those with the DD genotype had a significantly shorter time interval from onset of diabetes to the initiation of dialysis (13.4 +/- 1.4 years) than those with ID (20.7 +/- 1.2 years, P < 0.01) or II genotypes (17.5 +/- 1.1 year, P < 0.01). Analysis of the clinical course of the three ACE genotypes revealed that the majority (95%) of patients with the DD genotype who had albuminuria progressed to end-stage renal disease within 10 years of diagnosis of diabetes. Our analysis also revealed that initiation and continuation of dialysis are associated with a progressive decrease in the frequency of the DD genotype. These results indicate that, in NIDDM, the ACE DD genotype has a high prognostic value for progressive deterioration of renal function. Moreover, the DD genotype appears to increase the mortality once dialysis is initiated.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Albuminuria / complications
  • Albuminuria / enzymology
  • Albuminuria / genetics
  • Alleles
  • Base Sequence
  • DNA Primers / genetics
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / enzymology*
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetic Nephropathies / complications
  • Diabetic Nephropathies / enzymology
  • Diabetic Nephropathies / genetics
  • Female
  • Gene Frequency
  • Genotype
  • Humans
  • Japan
  • Kidney Failure, Chronic / complications
  • Kidney Failure, Chronic / enzymology
  • Kidney Failure, Chronic / genetics
  • Male
  • Middle Aged
  • Peptidyl-Dipeptidase A / genetics*
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Prognosis
  • Time Factors


  • DNA Primers
  • Peptidyl-Dipeptidase A