Association between the RAGE (receptor for advanced glycation end-products) -374T/A gene polymorphism and diabetic retinopathy in T2DM

Abstract

This meta-analysis reveals that the A allele of RAGE -374T/A polymorphism probably increase DR risk.

Association analysis of 374T/A (rs1800624) receptor for advanced glycation end-products (RAGE) gene polymorphism with diabetic retinopathy in Pakistani patients

“… 11 A notable association of mutant A allele with elevated risk of DR was also found in Caucasian and Asian populations. 4 …”

“…11 A notable association of mutant A allele with elevated risk of DR was also found in Caucasian and Asian populations. 4 Table-II: Association analysis of genotype distribution of 374T/A polymorphism among DNR, NPDR and PDR Groups. In contrast to this, various studies carried out in Asians, Caucasians, Chinese and Malaysians revealed no meaningful association of diabetic retinopathy with rs1800624 polymorphism.…”

“…It has been assessed for its association with DR in Asian, Caucasian, Indian, Malaysian and other populations. 2,4,5 Literature on the genetic factors involved in pathogenesis of DM and DR in Pakistani patients is very inadequate [6][7][8] and it is important to explore these factors to provide adequate and prompt therapy.…”

Oxidative Stress as the Main Target in Diabetic Retinopathy Pathophysiology

“…A state of sustained hyperglycemia can promote protein and lipid glycation in consequence producing AGE, which promote the alteration of the structure and function of other proteins; AGE has affinity for receptors known as receptor for advanced glycation end product (RAGE). The RAGEs are immunoglobulins that when activated promote the secretion of cytokines, which further stimulate the complications of diabetes by increasing vascular permeability and inflammatory processes [105, 106]. These effects will promote a hypoxic state in the microcapillaries of the retina leading to the beginning of the angiogenic process in the PDR [106].…”

“…The RAGEs are immunoglobulins that when activated promote the secretion of cytokines, which further stimulate the complications of diabetes by increasing vascular permeability and inflammatory processes [105, 106]. These effects will promote a hypoxic state in the microcapillaries of the retina leading to the beginning of the angiogenic process in the PDR [106]. It has also been found that AGEs and RAGE are overexpressed in DR, which leads to think that genetic polymorphisms of RAGE are probably involved in the DR pathophysiology [107].…”