Relations between ACE gene and ecNOS gene polymorphisms and resistive index in type 2 diabetic patients with nephropathy.
OBJECTIVE
ACE and endothelial cell nitric oxide synthase (ecNOS) genotypes have been reported to be related to the incidence of renal diseases and coronary artery diseases. In order to assess the effect of the gene polymorphism of both ACE and ecNOS on renal hemodynamic abnormality, we examined 155 Japanese patients with type 2 diabetes with various stages of nephropathy.


METHODS
The patients ranged in age from 40 to 72 years (92 men and 63 women). They were divided into four groups: group 1 consisted of patients with urinary albumin excretion (UAE) <30 mg/day (n = 69), group 2 had 30 < or = UAE < 300 mg/day (n = 44), group 3 had UAE > or =300 mg/day and serum creatinine <1.5 mg/dl (n = 22), and group 4 had serum creatinine >1.5 mg/dl (n = 20). Intrarenal hemodynamics were studied by duplex Doppler sonography in patients with type 2 diabetes. The ACE and ecNOS gene polymorphisms were examined by polymerase chain reaction.


RESULTS
There were no significant differences in sex, BMI, and blood glucose level, but there were differences in HbA(1c) and lipoprotein profiles among the four groups. There were no significant differences in the distribution of ACE genotype or in the frequency of the ecNOS 4a allele among the four groups. Resistive index (RI) values of the interlobar arteries of group 4 were significantly higher than those of groups 1, 2, and 3, whereas the RI values were not significantly different among groups 1, 2, and 3. Multiple regression analysis showed that age, duration of diabetes, systolic and diastolic blood pressure, and creatinine clearance were significantly associated with the increased RI values, but that there was no significant association between RI values and the ecNOS genotype (R(2) = 0.613, P < 0.0001).


CONCLUSIONS
These results suggest that intrarenal hemodynamic abnormalities are present as a feature of the progression of nephropathy in type 2 diabetes, and that they are associated with age, duration of diabetes, decreased creatinine clearance, and blood pressure, but not with the genetic factors of the ACE and ecNOS gene polymorphism in nephropathy of type 2 diabetes.
Taniwaki
H
H
Second Department of Internal Medicine, Osaka City University Medical School, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
Ishimura
E
E
Matsumoto
N
N
Emoto
M
M
Inaba
M
M
Nishizawa
Y
Y
D000328:Adult; D000368:Aged; D000419:Albuminuria; D044466:Asian People / Q000235:genetics; D001794:Blood Pressure; D003404:Creatinine / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D012077:Renal Artery / Q000503:physiopathology; D012079:Renal Circulation / Q000502:physiology; D018616:Ultrasonography, Doppler, Duplex; D014655:Vascular Resistance / Q000235:genetics*
D003404:Creatinine; D006442:Glycated Hemoglobin; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D007703:Peptidyl-Dipeptidase A; C496314:NOS3 protein, human