Gly82Ser Polymorphism of the Receptor for Advanced Glycation End Products Gene (RAGE) and the Endogenous Secretory RAGE (esRAGE) and its Association with Diabetic Retinopathy in Type 2 Diabetic Patients

The binding of advanced glycation end-products (AGEs) to their receptor (RAGE)
may play an important role in the development of diabetic retinopathy (DR). Recently,
endogenous secretory RAGE (esRAGE) has been identified as an alternative splicing
form of RAGE able to capture AGEs, and exerts protection against AGEs-induced
endothelial cell injury. A Gly82Ser polymorphism in exon 3 of RAGE gene was
identified and thought to have an effect on the functions of its protein. This study was
planned to investigate the frequency of the Gly82Ser polymorphism in RAGE gene
and the role of esRAGE as a biological marker for DR in type2 diabetes and its
association with the severity of DR. Thirty-five patients with type2 diabetes were
recruited into the study. They were subclassified into 15 patients with no clinically
apparent retinopathy (No DR), 12 patients with nonproliferative DR (NPDR), and 8
patients with proliferative DR (PDR). Twenty, age matched, healthy subjects were
included as controls. Serum esRAGE level was measured by enzyme-linked
immunosorbent assay. Genotype frequencies of Gly82Ser polymorphism were studied
by polymerase chain reaction amplification and restriction fragment length
polymorphism analysis using AluI enzyme. The results showed no significant
difference between serum esRAGE levels in both controls and diabetic patients with
No DR (P = 0.15). Among the diabetic subjects, there was a significant decrease of
serum esRAGE levels between patients with No DR and patients with NPDR (P =
0.008) and a more significant decrease between diabetic patients with No DR and
patients with PDR (P = 0.001). The low serum esRAGE diabetic patients had higher
risk to develop DR than those with high serum esRAGE level (odds ratio = 4.7, 95%
confidence interval = 1.07-20.65, P = 0.02). There were no significant differences in
genotyping frequencies or allele frequencies between controls and diabetic patients
with No DR, or patient with DR (P<0.05). In conclusion, serum esRAGE level showed
a significant association with the severity of DR and, hence, it could be used as a
prognostic tool to predict the development and progression of DR. esRAGE could be
a novel and potential protective factor for DR. Gly82Ser polymorphisms in RAGE
gene are not associated with the susceptibility of type 2 diabetes, or with the
development of DR in type 2 diabetic subjects.