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 > 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.
Yoshida
H
H
Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
Kuriyama
S
S
Atsumi
Y
Y
Tomonari
H
H
Mitarai
T
T
Hamaguchi
A
A
Kubo
H
H
Kawaguchi
Y
Y
Kon
V
V
Matsuoka
K
K
Ichikawa
I
I
Sakai
O
O
D000419:Albuminuria / Q000150:complications / Q000201:enzymology / Q000235:genetics; D000483:Alleles; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000201:enzymology* / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000150:complications / Q000201:enzymology / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007564:Japan; D007676:Kidney Failure, Chronic / Q000150:complications / Q000201:enzymology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011379:Prognosis; D013997:Time Factors
D017931:DNA Primers; D007703:Peptidyl-Dipeptidase A