Nitric Oxide Synthase Glu298Asp Polymorphism Research Articles

Endothelial Nitric Oxide Synthase Glu298Asp Polymorphism as a Risk Factor for Prostate Cancer

The endothelial form of nitric oxide synthases (eNOS) seems to have an important role in vascular development, maintenance of the vascular tone and tumor growth in human prostate cancer (PC). The purpose of this study was to investigate the association between grade and stage of disease, age of diagnosis, vascular or perineural invasion, pre-diagnostic plasma prostate-specific antigen (PSA) levels, prostate cancer risk and Glu298Asp polymorphism of the eNOS gene. Ninety-five prostate cancer patients and 111 benign prostate hyperplasia subjects were included. The Glu298Asp polymorphism of the eNOS gene was determined by polymerase chain reaction and restriction fragment length polymorphism The odds ratio (OR) between the GT and GG polymorphism was 0.76, indicating that the presence of the GT polymorphism decreased the risk of prostate cancer of more than 20% compared to the GG polymorphism. This difference, however, was not statistically significant. The GT polymorphism had an inverse association with cancer grade compared to the reference group (OR=0.47, p value=0.2). These results suggest that prostate cancer development is not associated with the Glu298Asp polymorphism of the endothelial nitric oxide synthase gene in our population. Further studies in larger samples are needed to confirm our results and characterize the molecular mechanisms by which eNOS is involved in the susceptibility to prostate cancer.

Impact of Nitric Oxide Synthase Glu298Asp Polymorphism on the Development of End-Stage Renal Disease in Type 2 Diabetic Egyptian Patients

Background: Nitric oxide is an important regulator of renal hemodynamics. This study aimed to investigate the role of endothelial nitric oxide synthase (eNOS) gene polymorphism in type 2 diabetic patients with end-stage renal disease (ESRD) and to elucidate any alteration of nitric oxide synthase (NOS) activity caused by this polymorphism. Methods: The study included 80 patients with type 2 diabetes of >10 years duration (40 with diabetes-derived ESRD, 40 without nephropathy) and 20 healthy controls. Plasma nitrate/nitrite level, and serum NOS activity were measured and eNOS Glu298Asp genotypes were determined. Results: The frequency of Glu/Glu (GG) genotype in diabetics with ESRD was lower than controls. However, the frequency of Asp/Asp (TT) genotype was increased in diabetics with ESRD as compared to those without nephropathy and controls. Diabetics with ESRD had significantly lower nitrate/nitrite level and NOS activity than those without nephropathy. Diabetic patients with TT genotype are at a significant risk for ESRD. Moreover, subjects carrying TT genotype had lower nitrate/nitrite level and NOS activity than those carrying GG genotype. In diabetics with ESRD, creatinine clearance was positively correlated with both nitrate/nitrite level and NOS activity. Conclusions: These results imply that TT genotype of eNOS may be associated with an increased risk of ESRD in Egyptian type 2 diabetics. It could represent a useful genetic marker to identify diabetics at high risk for the development of ESRD. However, larger future prospective studies are required to confirm the role of eNOS gene polymorphism in the progression of diabetic nephropathy to ESRD.

Effect of the endothelial nitric oxide synthase Glu298Asp polymorphism on endothelial function and lipid profile in healthy subjects

Effect of the endothelial nitric oxide synthase Glu298Asp polymorphism on endothelial function and lipid profile in healthy subjects

Association of endothelial nitric oxide synthase Glu298Asp polymorphism with end-stage renal disease

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). 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). 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. It appears that Glu298Asp may be a predisposing factor in DM-derived and HT-derived ESRD.

The endothelial nitric oxide synthase Glu298Asp polymorphism is not a risk factor for endometriosis in south Indian women

Objective To investigate whether the eNOS gene influences the risk of developing endometriosis in south Indian women. Study design The single nucleotide polymorphism, Glu298Asp, in exon7 of the eNOS gene was tested for association in a case–control study of 232 affected women and 210 women with no evidence of disease. All the women were infertile, ascertained from the same infertility clinic. The genotype frequencies of the polymorphism were compared, using polymerase chain reaction and sequencing analysis. The localization and expression of eNOS in the eutopic endometrium of five cases and four controls was also analyzed using immunohistochemistry and western blotting. Results No statistically significant differences were observed in the genotype distributions and allele frequencies ( p = 0.3) between the cases and controls according to codominant, dominant and recessive genotype models. The localization and expression of this protein were similar in the endometrium of cases and controls. Conclusion In the present study we could neither observe a difference in the eNOS expression nor establish an association between the eNOS Glu298Asp exon 7 polymorphism in south Indian women with endometriosis.

The Influence of G‐Protein β3‐Subunit Gene and Endothelial Nitric Oxide Synthase Gene in Exon 7 Polymorphisms on Progression of Autosomal Dominant Polycystic Kidney Disease

Background: A significant phenotypical variability is observed in autosomal dominant polycystic kidney disease (ADPKD). The variability cannot be fully explained by the genetic heterogeneity of the disease. We examined the influence of G‐protein β3‐subunit C825T polymorphism and endothelial nitric oxide synthase Glu298Asp polymorphism on the progression of ADPKD towards end stage renal failure (ESRF). Methods: 306 ADPKD patients (pts) were analyzed; 261 pts (136 males, 125 females) with ESRF, with subgroup of 73 pts (44 males, 29 females) with ESRF before 45 years (rapid progressors), 46 pts (20 males, 26 females) with ESRF later than in 63 years (slow progressors) and 45 ADPKD pts (17 males, 28 females) in mean age 51 years with serum creatinine under 110 µmol/L (slow progressors) and 100 genetically unrelated healthy Czech subjects. DNA samples from collected blood were genotyped for G‐protein β3‐subunit C825T genotype in exon 10 and for endothelial nitric oxide synthase Glu298Asp genotype in exon 7. Results: The G‐protein β3‐subunit C825T genotype exhibited no significant differences among the groups of slow progressors (6.6% (6/91) TT, 54.9% (50/91) CT, 38.8% (35/91) CC), rapid progressors (9.6% (7/73) TT, 46.6% (34/73) CT, 43.8% (32/73) CC), ADPKD group with ESRF between 40–63 years (9.2% (13/142) TT, 50% (71/142) CT, 40.8% (58/142) CC) and control group (12% TT, 44% CT, 44% CC). When comparing the ages of ESRF of all patients with ESRF, we did not find significant differences in the ages: males TT—51.7 ± 8.8 years, CT—51.9 ± 10.3 years, CC—49.7 ± 10.2 years and females TT—56 ± 9.9 years, CT—53.2 ± 8.5 years, CC—53.9 ± 8.7 years. The endothelial nitric oxide synthase Glu298Asp and Asp29Asp genotypes were significantly more frequent in rapid progressors (9.6% (7/73) Asp/Asp, 39.7% (29/73) Asp/Glu, 50.7% (37/73) Glu/Glu) and in ADPKD group with ESRF between 40–63 years (11.3% (16/142) Asp/Asp, 41.5% (59/142) Asp/Glu, 47.2% (67/142) Glu/Glu) in comparison with slow progressors (8.8% (8/91) Asp/Asp, 24.2% (22/91) Asp/Glu, 67.0% (61/91) Glu/Glu) and with control group (8% Asp/Asp, 32% Asp/Glu, 60% Glu/Glu) (Chi‐square test, p < 0.05). Comparing the ages of ESRF of all patients with ESRF, we did not find significant differences in the ages in males with Asp/Asp—54.9 ± 10.4 years, Asp/Glu—50.2 ± 9.4 years, Glu/Glu—51.0 ± 10.4 years. We found out in homozygous Asp/Asp females significantly earlier onset of ESRF (49.2 ± 5.6 years) in comparison with heterozygous females (53.3 ± 7.2 years) and with Glu/Glu homozygous females (54.8 ± 9.7 years) (t‐test, p < 0.05). Conclusion: We excluded the significance of G‐protein β3‐subunit C825T polymorphism on the progression of ADPKD. We established the negative prognostic value of the carriers of Asp variant of eNOS polymorphism. Finding of new modifiers could have in future clinical consequences for ADPKD patients.

Endothelial nitric oxide synthase GLU298ASP polymorphism and blood pressure responses to salt

Clinical Pharmacology &amp; Therapeutics (2003) 73, P98–P98; doi: