Endothelial nitric oxide synthase intron 4 polymorphism influences the progression of renal disease.
OBJECTIVE
Nitric oxide is a potent regulator of intrarenal hemodynamics and may influence the renal function. We investigated whether polymorphism of intron 4 of the endothelial constitutive nitric oxide synthase (ecNOS) gene is related to the progression of chronic renal failure.


METHODS
Polymorphism of ecNOS intron 4 was studied in 1,005 hemodialysis patients (710 with nondiabetic nephropathy and 295 with diabetic nephropathy) and was compared with the findings in 189 healthy subjects. ecNOS genotypes were determined by the polymerase chain reaction, followed by agarose gel electrophoresis.


RESULTS
The frequencies of ecNOS4a/a, ecNOS4a/b, and ecNOS4b/b genotypes were, respectively, 0% (0/189), 13.8% (26/189), and 86.2% (163/189) in the control group; 1.7% (12/710), 22.1% (157/710), and 76.2% (541/710) in the nondiabetic nephropathy group, and 1.0% (3/295), 22.7% (67/295), and 76.3% (225/295) in the diabetic nephropathy group. The frequency of ecNOS4a (ecNOSa/a and ecNOSa/b) was significantly higher in both the nondiabetic group and in the diabetic group than in the controls (p = 0.0025 and p = 0.0438, respectively).


CONCLUSIONS
There was a significantly higher frequency of the a allele of intron 4 in both nondiabetic and diabetic hemodialysis patients, so the polymorphism of intron 4 of the ecNOS gene may have a wide influence on the progression of renal disease.
Asakimori
Y
Y
2nd Department of Internal Medicine, Hiroshima University School of Medicine, Hiroshima, Japan.
Yorioka
N
N
Yamamoto
I
I
Okumoto
S
S
Doi
S
S
Hirai
T
T
Taniguchi
Y
Y
D000328:Adult; D000368:Aged; D003928:Diabetic Nephropathies / Q000201:enzymology / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006801:Humans; D007438:Introns; D007676:Kidney Failure, Chronic / Q000201:enzymology / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D011110:Polymorphism, Genetic
C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III