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

• Published in: Kidney international Vol. 50; no. 2; pp. 657 - 664
• Main Authors: Yoshida, Hiroaki, Kuriyama, Satoru, Atsumi, Yoshihito, Tomonari, Haruo, Mitarai, Tetsuya, Hamaguchi, Akihiko, Kubo, Hitoshi, Kawaguchi, Yoshindo, Kon, Valentina, Matsuoka, Kenpei, Ichikawa, Iekuni, Sakai, Osamu
• Format: Journal Article Conference Proceeding
• Language: English
• Published: New York, NY Elsevier Inc 01.08.1996; Nature Publishing
• Subjects: Albuminuria - complications; Albuminuria - enzymology; Albuminuria - genetics; Alleles; Associated diseases and complications; Base Sequence; Biological and medical sciences; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - enzymology; Diabetes Mellitus, Type 2 - genetics; Diabetes. Impaired glucose tolerance; Diabetic Nephropathies - complications; Diabetic Nephropathies - enzymology; Diabetic Nephropathies - genetics; DNA Primers - genetics; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Female; Gene Frequency; Genotype; Humans; Japan; Kidney Failure, Chronic - complications; Kidney Failure, Chronic - enzymology; Kidney Failure, Chronic - genetics; Male; Medical sciences; Middle Aged; Peptidyl-Dipeptidase A - genetics; Polymerase Chain Reaction; Polymorphism, Genetic; Prognosis; Time Factors; Japan; Endocrinopathy; Human; Urinary system disease; Genetic inheritance; Renal function; Prognosis; Enzyme; Renal disease; Exploration; Non insulin dependent diabetes; Concomitant disease; Gene; Peptidyl-dipeptidase A; Renal failure; Hydrolases; Peptidyl-dipeptidases; Complication; Proteinases
• ISSN: 0085-2538; 1523-1755
• DOI: 10.1038/ki.1996.362

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