![](/images/graphics-bg.png)
Protective Effect of the HIF-1A Pro582Ser Polymorphism on Severe Diabetic Retinopathy
Joint Authors
Falhammar, Henrik
Catrina, Sergiu
Ekberg, Neda Rajamand
Eliasson, Sofie
Li, Young Wen
Zheng, Xiaowei
Chatzidionysiou, Katerina
Gu, Harvest F.
Source
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-8, 8 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-05-12
Country of Publication
Egypt
No. of Pages
8
Main Subjects
Abstract EN
Objective.
Hypoxia is central in the pathogenesis of diabetic retinopathy (DR).
Hypoxia-inducible factor-1 (HIF-1) is the key mediator in cellular oxygen homeostasis that facilitates the adaptation to hypoxia.
HIF-1 is repressed by hyperglycemia contributing by this to the development of complications in diabetes.
Recent work has shown that the HIF-1A Pro582Ser polymorphism is more resistant to hyperglycemia-mediated repression, thus protecting against the development of diabetic nephropathy.
In this study, we have investigated the effect of the HIF-1A Pro582Ser polymorphism on the development of DR and further dissected the mechanisms by which the polymorphism confers a relative resistance to the repressive effect of hyperglycemia.
Research Design and Method.
703 patients with type 1 diabetes mellitus from one endocrine department were included in the study.
The degree of retinopathy was correlated to the HIF-1A Pro582Ser polymorphism.
The effect of glucose on a stable HIF-1A construct with a Pro582Ser mutation was evaluated in vitro.
Results.
We identified a protective effect of HIF-1A Pro582Ser against developing severe DR with a risk reduction of 95%, even when adjusting for known risk factors for DR such as diabetes duration, hyperglycemia, and hypertension.
The Pro582Ser mutation does not cancel the destabilizing effect of glucose but is followed by an increased transactivation activity even in high glucose concentrations.
Conclusion.
The HIF-1A genetic polymorphism has a protective effect on the development of severe DR.
Moreover, the relative resistance of the HIF-1A Pro582Ser polymorphism to the repressive effect of hyperglycemia is due to the transactivation activity rather than the protein stability of HIF-1α.
American Psychological Association (APA)
Ekberg, Neda Rajamand& Eliasson, Sofie& Li, Young Wen& Zheng, Xiaowei& Chatzidionysiou, Katerina& Falhammar, Henrik…[et al.]. 2019. Protective Effect of the HIF-1A Pro582Ser Polymorphism on Severe Diabetic Retinopathy. Journal of Diabetes Research،Vol. 2019, no. 2019, pp.1-8.
https://search.emarefa.net/detail/BIM-1172863
Modern Language Association (MLA)
Ekberg, Neda Rajamand…[et al.]. Protective Effect of the HIF-1A Pro582Ser Polymorphism on Severe Diabetic Retinopathy. Journal of Diabetes Research No. 2019 (2019), pp.1-8.
https://search.emarefa.net/detail/BIM-1172863
American Medical Association (AMA)
Ekberg, Neda Rajamand& Eliasson, Sofie& Li, Young Wen& Zheng, Xiaowei& Chatzidionysiou, Katerina& Falhammar, Henrik…[et al.]. Protective Effect of the HIF-1A Pro582Ser Polymorphism on Severe Diabetic Retinopathy. Journal of Diabetes Research. 2019. Vol. 2019, no. 2019, pp.1-8.
https://search.emarefa.net/detail/BIM-1172863
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1172863