Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2817191 | Gene | 2013 | 7 Pages |
•RAGE polymorphism 2245G/A & pro-inflammatory markers in DR patients were examined.•DR patients had significantly higher frequency of 2245A allele than DNR patients.•2245GA DR patients had higher NF-κB, MCP-1 & AOPP levels than 2245GG DR patients.•Significantly lower sRAGE level in 2245GA DR patient versus 2245GG DR patients.•RAGE gene polymorphism 2245G/A could aggravate DR in patients via NF-κB pathway.
BackgroundReceptor for advanced glycation end-product (RAGE) gene polymorphism 2245G/A is associated with diabetic retinopathy (DR). However, the mechanism on how it affects the disease development is still unclear.AimThis study aims to investigate the relationship between 2245G/A RAGE gene polymorphism and selected pro-inflammatory, oxidative-glycation markers in DR patients.MethodsA total of 371 unrelated type 2 diabetic patients [200 with retinopathy, 171 without retinopathy (DNR)] and 235 healthy subjects were recruited. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism method followed by DNA sequencing. The nuclear and cytosolic extracts from peripheral blood mononuclear cells were used for nuclear factor kappa B (NF-κB) p65 and superoxide dismutase activity measurement respectively. Plasma was used for glutathione peroxidase activity, advanced oxidation protein product (AOPP), monocyte chemoattractant protein (MCP)-1, pentosidine and soluble RAGE (sRAGE) measurements.ResultsDR patients with 2245GA genotype had significantly elevated levels of activated NF-κB p65, plasma MCP-1, AOPP and pentosidine but lower level of sRAGE when compared to DR patients with wild-type 2245GG.ConclusionThe RAGE gene polymorphism 2245G/A is associated with pro-inflammatory, oxidative-glycation markers and circulating sRAGE in DR patients. Patients with 2245GA RAGE genotype could aggravate DR possibly via NF-κB mediated inflammatory pathway.