Association of endothelial nitric oxide synthase Glu298Asp, 4b/a, and −786T&gt;C gene variants with diabetic nephropathy

Ezzidi, Intissar; Mtiraoui, Nabil; Mohamed, Manel Ben Hadj; Mahjoub, Touhami; Kacem, M.; Almawi, Wassim Y.

doi:10.1016/j.jdiacomp.2007.11.011

Cited by 81 publications

(62 citation statements)

References 42 publications

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“…Finally, our results show a significantly higher prevalence of the eNOS 4a allele in diabetics in comparison to non-diabetic ACS patients, so confirming data from literature reporting its role in increasing susceptibility to both diabetes and its complications [23,24].…”

Section: Discussionsupporting

confidence: 90%

Platelet aggregability is modulated by eNOS locus in non-type 2 diabetic patients with acute coronary syndrome☆

Fatini¹,

Sticchi²,

Bolli³

et al. 2011

Nutrition, Metabolism and Cardiovascular Diseases

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Background and aim: Platelet nitric oxide (NO) synthesis is compromised in patients with acute coronary syndrome (ACS), and platelet NO availability may be critically relevant in determining the extent of thrombosis in ACS patients. It has been demonstrated that an impaired responsiveness to the antiaggregatory effects of NO may affect platelet dysfunction in diabetic patients with ACS. Since NO availability may be genetically determined, we have investigated the role of endothelial nitric oxide synthase (eNOS) gene in influencing platelet aggregability in relation to the presence (n Z 247) or absence (n Z 883) of type 2 diabetes in ACS patients. Methods and results: We have genotyped 1130 consecutive high risk ACS patients on dual antiplatelet therapy, previously investigated in relation to platelet function. eNOS 4a allele frequency was significantly higher in diabetic vs. non-diabetic patients (p Z 0.02). In non-diabetic patients the eNOS 4a allele significantly modulated platelet aggregability in response to arachidonic acid (AA), but not to collagen and adenosine diphosphate (ADP) stimulus, after Bonferroni correction for multiple testing. After adjustment for age, gender, smoking habit, hypertension and ejection fraction 40%, the eNOS 4a allele remained significantly and independently associated with platelet aggregability in response to AA stimulus [b (SE) Z 0.17 (0.07), p Z 0.01]. When platelet aggregation values were considered according to the presence or absence of high residual platelet reactivity (RPR) eNOS 4a, but not À786C and 894T, allele was significantly associated with RPR by AA stimulus. The haplotype reconstruction analysis for eNOS gene showed that the À786C/894G/4a and À786C/894G/4b haplotypes significantly influenced platelet aggregation after AA stimulus. Conclusions: Our study indicates that eNOS 4a allele, may be a determinant of higher platelet aggregability and residual platelet reactivity in non-diabetic ACS patients. ª

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Section: Discussionsupporting

confidence: 90%

Platelet aggregability is modulated by eNOS locus in non-type 2 diabetic patients with acute coronary syndrome☆

Fatini¹,

Sticchi²,

Bolli³

et al. 2011

Nutrition, Metabolism and Cardiovascular Diseases

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“…These notions were supported by recent reports. 34,35 In studies by Noiri et al, 36 and Thaha et al, 37 it is indicated that eNOS Glu298Asp polymorphism is the predisposing factor in ESRD, especially DM-derived ESRD. Moreover, Zanchi et al, 38 and Mollsten et al 39 suggested an association between eNOS polymorphism and the risk of DN in patients with type 1 diabetes.…”

Section: Discussionmentioning

confidence: 99%

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

Bessa

Hamdy

2011

Renal Failure

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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.

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“…Three polymorphisms in this gene G894T missense mutation (rs1799983), a 27-bp repeat in intron 4, and the T786C single nucleotide polymorphism (SNP) in the promoter (rs2070744) have been found to be associated with diabetic nephropathy susceptibility [26][27][28][29][30] . The G894T variant was found to increase the risk of macroalbuminuria and progression from microalbuminuria to macroalbuminuria, with declining glomerular filtration rate as serum creatinine value rises progressively, culminating in nephropathy [31,32] However, these results have been contradictory and not all studies support this association [33][34][35] .…”

Section: Gene Variants Of Renal Function Componentsmentioning

confidence: 99%

Association of genetic variants with diabetic nephropathy

Rizvi

Raza

Mahdi

2014

WJD

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Association of endothelial nitric oxide synthase Glu298Asp, 4b/a, and −786T>C gene variants with diabetic nephropathy

Cited by 81 publications

References 42 publications

Platelet aggregability is modulated by eNOS locus in non-type 2 diabetic patients with acute coronary syndrome☆

Platelet aggregability is modulated by eNOS locus in non-type 2 diabetic patients with acute coronary syndrome☆

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

Association of genetic variants with diabetic nephropathy

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