Association of endothelial nitric oxide synthase Glu298Asp polymorphism with end-stage renal disease.
BACKGROUND
Impairment of nitric oxide generation caused by gene polymorphism is considered as a major factor in the deterioration of progressive renal disease, including diabetic nephropathy and hypertension. The aim of the present study was to examine the Glu298Asp polymorphism of endothelial nitric oxide synthase (eNOS) in patients with end-stage renal disease (ESRD).


METHODS
The Glu298Asp polymorphism in exon 7 was determined in 100 ESRD patients who were maintained on hemodialysis at Dr. Soetomo Hospital, Surabaya, Indonesia, and in a control group of 100 unrelated healthy individuals. In the patient group, 39 patients had Type 2 diabetes mellitus (DM), 44 hypertension (HT) and 17 miscellaneous conditions. The mean length of time from onset of ESRD to the start of this study was 24.37 +/- 32.37 months (Mean +/- SD).


RESULTS
The positivity of Glu298Asp in the ESRD group was significantly higher than that in the control group (p < 0.0001). The odds ratio for this group was 4.57 (95% confidence interval 2.52 - 8.31). The positivity of 298Asp in Type 2 DM ESRD with subgroup was significantly higher than that in healthy controls (p < 0.0001). The positivity of 298Asp in the subgroup of patients with HT-derived ESRD was also significantly higher (males p < 0.036, females p < 0.005) than that in healthy control group. Homozygotes with glutamate to aspartate substitution at nucleotide position 7702 showed a single band at 457 bp.


CONCLUSIONS
It appears that Glu298Asp may be a predisposing factor in DM-derived and HT-derived ESRD.
Thaha
M
M
Department of Internal Medicine, Division of Nephrology-Hypertension, Airlangga University School of Medicine, Surabaya, Indonesia.
Pranawa
Yogiantoro
M
M
Sutjipto
Sunarjo
Tanimoto
M
M
Gohda
T
T
Tomino
Y
Y
D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics; D007676:Kidney Failure, Chronic / Q000201:enzymology / Q000235:genetics* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000097:blood / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D006435:Renal Dialysis; D018709:Statistics, Nonparametric
D015415:Biomarkers; D052250:Nitric Oxide Synthase Type III