Dataset Information

Association of the endothelial nitric oxide synthase (eNOS) 4a/b polymorphism with the risk of incident diabetic retinopathy in patients with type 2 diabetes mellitus: a systematic review and updated meta-analysis.

ABSTRACT:

Objective

To conduct a systematic review and updated meta-analysis on the potential association between endothelial nitric oxide synthase (eNOS) 4a/b polymorphism and the risk of developing diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM) and to identify possible clinical biomarkers for early screening of DR.

Materials and methods

A meta-analysis based on case-control or cross-sectional studies was conducted to examine the correlation between eNOS 4a/b polymorphism and DR. Pooled odds ratio (OR) and 95% confidence interval (CI) were used to estimate the association strength.

Results

We included 19 studies, covering 7838 subjects. An association was observed in Caucasians (allelic model: OR = 1.273, 95% CI: 1.006-1.610, p = .045; recessive model: OR = 0.575, 95% CI: 0.371-0.892, p = .014; dominant model: OR = 1.268, 95% CI: 1.052-1.528, p = .013; homozygote model: OR = 1.833, 95% CI: 1.176-2.856, p = .007). Moreover, population-based studies have indicated an association between eNOS 4a/b polymorphism and DR susceptibility.

Conclusions

The present study showed that intron 4a allele of eNOS 4a/b is a risk factor for DR in Caucasians with T2DM. Thus, eNOS 4a/b may be used as a biomarker for the early screening and diagnosis of DR in Caucasian T2DM patients.Key messagesEndothelial nitric oxide synthase 4a/b gene polymorphism is not associated with the risk of developing diabetic retinopathy in the overall population, Asians, or Chinese Han patients with type 2 diabetes. However, 4a is a risk factor for the development of diabetic retinopathy in Caucasians.Endothelial nitric oxide synthase 4a/b gene polymorphism is not associated with the type of diabetic retinopathy.

SUBMITTER: Shi Y

PROVIDER: S-EPMC10291908 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Publications

Association of the endothelial nitric oxide synthase (eNOS) 4a/b polymorphism with the risk of incident diabetic retinopathy in patients with type 2 diabetes mellitus: a systematic review and updated meta-analysis.

Shi Yushan Y Fan Xin X Zhang Kaiyun K Ma Yaling Y

Annals of medicine 20231201 1

<h4>Objective</h4>To conduct a systematic review and updated meta-analysis on the potential association between endothelial nitric oxide synthase (eNOS) 4a/b polymorphism and the risk of developing diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM) and to identify possible clinical biomarkers for early screening of DR.<h4>Materials and methods</h4>A meta-analysis based on case-control or cross-sectional studies was conducted to examine the correlation between eNOS 4a/b po ...[more]

PMID: 37353997

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Project description:Compelling evidence suggests a role for the inducible nitric oxide synthase, iNOS, and the bradykinin type 1 receptor (B1R) in diabetic retinopathy, including a possible control of the expression and activity of iNOS by B1R. In diabetic retina, both iNOS and B1R contribute to inflammation, oxidative stress, and vascular dysfunction. The present study investigated whether inhibition of iNOS has any impact on inflammatory/oxidative stress markers and on the B1R-iNOS expression, distribution, and action in a model of type I diabetes. Diabetes was induced in 6-week-old Wistar rats by streptozotocin (65 mg.kg-1, i.p.). The selective iNOS inhibitor 1400W (150 μg.10 μl-1) was administered twice a day by eye-drops during the second week of diabetes. The retinae were collected 2 weeks after diabetes induction to assess the protein and gene expression of markers by Western blot and qRT-PCR, the distribution of iNOS and B1R by fluorescence immunocytochemistry, and the vascular permeability by the Evans Blue dye technique. Diabetic retinae showed enhanced expression of iNOS, B1R, carboxypeptidase M (involved in the biosynthesis of B1R agonists), IL-1β, TNF-α, vascular endothelium growth factor A (VEGF-A) and its receptor, VEGF-R2, nitrosylated proteins and increased vascular permeability. All those changes were reversed by treatment with 1400W. Moreover, the additional increase in vascular permeability in diabetic retina induced by intravitreal injection of R-838, a B1R agonist, was also prevented by 1400W. Immunofluorescence staining highlighted strong colocalization of iNOS and B1R in several layers of the diabetic retina, which was prevented by 1400W. This study suggests a critical role for iNOS and B1R in the early stage of diabetic retinopathy. B1R and iNOS appear to partake in a mutual auto-induction and amplification loop to enhance nitrogen species formation and inflammation in diabetic retina. Hence, B1R-iNOS axis deserves closer scrutiny in targeting diabetic retinopathy.

Dataset Information

Association of the endothelial nitric oxide synthase (eNOS) 4a/b polymorphism with the risk of incident diabetic retinopathy in patients with type 2 diabetes mellitus: a systematic review and updated meta-analysis.

Objective

Materials and methods

Results

Conclusions

Publications

Association of the endothelial nitric oxide synthase (eNOS) 4a/b polymorphism with the risk of incident diabetic retinopathy in patients with type 2 diabetes mellitus: a systematic review and updated meta-analysis.

Similar Datasets

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