Angiotensin-II type 1 receptor gene polymorphism and diabetic microangiopathy.
BACKGROUND
Genotypic abnormalities of the renin-angiotensin system have been suggested as risk factors for the development of hypertension, diabetic nephropathy and proliferative retinopathy. Most of the known actions of angiotensin-II are exerted through the angiotensin-II type 1 receptor, which is present particularly in vascular smooth muscle cells, myocardium and the kidney. A transversion of adenine to cytosine at nucleotide position 1166 in the gene coding for the angiotensin-II type 1 receptor has been associated with hypertension in the non-diabetic population.


METHODS
We studied the relationship between the A1166-->C polymorphism in the angiotensin-II type 1 receptor gene in patients with insulin dependent diabetes mellitus (IDDM) and diabetic nephropathy (121 men, 77 women, age 41 +/- 10 years, diabetes duration 27 +/- 8 years) and in IDDM patients with normoalbuminuria (116 men, 74 women, age 43 +/- 10 years, diabetes duration 27 +/- 8 years). 156 patients (40%) had proliferative retinopathy, 67 patients (17%) had no diabetic retinopathy.


RESULTS
There was no difference in genotype distribution between IDDM patients with diabetic nephropathy and normoalbuminuria 103 (52%) / 81 (41%) / 14 (7%) vs. 97 (51%) / 80 (42%) / 13 (7%) had AA/AC/CC genotypes, respectively. The allele frequencies (A/C) in patients with nephropathy (0.73/0.27) and patients with normoalbuminuria (0.72/0.28) were also similar. No difference in genotype distribution between IDDM patients with proliferative retinopathy and without diabetic retinopathy was found either: 77 (50%) / 66 (42%) / 13 (8%) vs. 42 (63%) / 22 (33%) / 3 (4%) had AA/AC/CC genotypes, respectively.


CONCLUSIONS
The A1166-->C polymorphism in the angiotensin-II type 1 receptor gene does not contribute to the genetic susceptibility to diabetic nephropathy or proliferative retinopathy in caucasian IDDM patients.
Tarnow
L
L
Steno Diabetes Center, Gentofte, Denmark.
Cambien
F
F
Rossing
P
P
Nielsen
F S
FS
Hansen
B V
BV
Ricard
S
S
Poirer
O
O
Parving
H H
HH
D000328:Adult; D000419:Albuminuria / Q000652:urine; D001483:Base Sequence; D016022:Case-Control Studies; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1; D003925:Diabetic Angiopathies / Q000150:complications / Q000235:genetics* / Q000652:urine; D003930:Diabetic Retinopathy / Q000150:complications; D005260:Female; D006801:Humans; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D011945:Receptors, Angiotensin / Q000235:genetics*; D012016:Reference Values
D015335:Molecular Probes; D011945:Receptors, Angiotensin