Single nucleotide variants of receptor for advanced glycation end-products (AGER) gene: is it a new opening in the risk assessment of diabetic retinopathy?-a review

BACKGROUND: Diabetic retinopathy (DR) is a common microvascular complication of diabetes. There is strong evidence suggesting that DR has an inheritable component. The interaction between advanced glycation end products (AGEs) and their receptor is integral in the pathogenesis of diabetic retinopathy and its various complications, retinopathy being one of them.

OVERVIEW AND METHODOLOGY: This review discusses the existing literature on the association between single nucleotide variants (SNV) of AGER gene and the risk of DR. It also discusses the current understanding of the AGE-AGER pathway in diabetic retinopathy. Through our article we have tried to consolidate all the available information about these SNVs associated with diabetic retinopathy in a succinct tabular form. Additionally, a current understanding of the AGE-AGER interaction and its deleterious effects on the cells of the retina has been discussed in detail to provide comprehensive information about the topic to the reader. A literature review was performed on PubMed, Cochrane Library, and Google Scholar for studies to find existing literature on the association between AGER gene SNVs and the risk, progression and severity of developing DR. This article will encourage scientific communication and discussion about possibly devising genetic markers for an important cause of blindness both in developed and developing countries, i.e., diabetic retinopathy.

RESULT: Based on genetic studies done in Indian and Chinese population G82S(rs2070600) was positively associated with Diabetic Retinopathy. Patients of diabetic retinopathy in Caucasian population had -T374A(rs1800624) polymorphism. + 20T/A was found to be associated with the disease in a study done in UK. Association with G1704T(rs184003) was seen in Chinese and Malaysian population. A Chinese study found its association with CYB242T. -T429C(rs1800625) SNV was not associated with DR in any of the studies. G2245A(rs55640627) was positively associated with the disease process in Malaysian population. It was not associated in Malaysian and Chinese population. Promoter variant rs1051993 has also been found to a susceptible SNV in the Chinese population.

CONCLUSION: While providing a comprehensive review of the existing information, we would like to emphasize on a large, multi-centric, trial with a much larger and varied population base to definitely determine these single nucleotide variants predisposing diabetic individuals.