title: Receptor for advanced glycation end-product (RAGE) gene polymorphism 2245G/A is associated with pro-inflammatory, oxidative-glycation markers and sRAGE in diabetic retinopathy.
abstract: BACKGROUND
  Receptor 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.
  
  
  OBJECTIVE
  This study aims to investigate the relationship between 2245G/A RAGE gene polymorphism and selected pro-inflammatory, oxidative-glycation markers in DR patients.
  
  
  METHODS
  A 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.
  
  
  RESULTS
  DR 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.
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Zhi Xiang
authors.initials: ZX
authors.lastname: Ng
authors.forename: Umah Rani
authors.initials: UR
authors.lastname: Kuppusamy
authors.forename: Tajunisah
authors.initials: T
authors.lastname: Iqbal
authors.forename: Kek Heng
authors.initials: KH
authors.lastname: Chua
mesh_terms: D000328:Adult; D062107:Advanced Oxidation Protein Products / Q000235:genetics / Q000378:metabolism; D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005838:Genotype; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000378:metabolism; D008239:Lysine / Q000031:analogs & derivatives / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D011110:Polymorphism, Genetic; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism
chemical_list: D062107:Advanced Oxidation Protein Products; D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D017127:Glycation End Products, Advanced; D016328:NF-kappa B; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D001120:Arginine; C062187:pentosidine; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D008239:Lysine