Lack of relationship between an insertion/deletion polymorphism in the angiotensin I-converting enzyme gene and diabetic nephropathy and proliferative retinopathy in IDDM patients.
Genotypic abnormalities of the renin-angiotensin system have been suggested as a risk factor for the development of diabetic nephropathy and proliferative retinopathy. We studied the relationship between an insertion(I)/deletion (D) polymorphism in the angiotensin-converting enzyme (ACE) gene in insulin-dependent diabetes mellitus (IDDM) patients with diabetic nephropathy (121 men and 77 women, age 40.9 +/- 10 years, diabetes duration 27 +/- 8 years) and in IDDM patients with normoalbuminuria (118 men and 74 women, age 42.7 +/- 10 years, diabetes duration 26 +/- 8 years). A total of 155 patients (40%) had proliferative retinopathy, and 67 patients (17%) had no diabetic retinopathy. There was no difference in genotype distribution between IDDM patients with diabetic nephropathy and those with normalbuminuria: 63 (32%)/95 (48%)/40 (20%) vs. 67 (35%)/77 (41%)/46 (24%) had DD/ID/II genotypes, respectively. Patients with nephropathy had higher plasma ACE levels (609 [151-1,504] micrograms/l) compared with patients with normoalbuminuria (428 [55-1,630] micrograms/l) (P < 0.001). Multiple linear regression analysis revealed that the plasma ACE level in patients with nephropathy is partially determined by ACE/ID polymorphism, mean arterial blood pressure, and glomerular filtration rate (r2 = 0.30, P < 0.001). There was no difference in genotype distribution between IDDM patients with proliferative retinopathy and those without diabetic retinopathy: 52 (34%)/74 (48%)/29 (19%) vs. 26 (39%)/25 (37%)/16 (24%) had DD/ID/II genotypes, respectively. There was also no difference in plasma ACE concentration detected among patients with no, simplex, or proliferative retinopathy.(ABSTRACT TRUNCATED AT 250 WORDS)
Tarnow
L
L
Steno Diabetes Center, Gentofte, Denmark.
Cambien
F
F
Rossing
P
P
Nielsen
F S
FS
Hansen
B V
BV
Lecerf
L
L
Poirier
O
O
Danilov
S
S
Parving
H H
HH
D000328:Adult; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000201:enzymology* / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000201:enzymology* / Q000235:genetics*; D003930:Diabetic Retinopathy / Q000201:enzymology* / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic
D007703:Peptidyl-Dipeptidase A