title: Soluble RAGE, diabetic nephropathy and genetic variability in the AGER gene.
abstract: Diabetes mellitus, especially when complicated with decline of renal function due to diabetic nephropathy (DN), is associated with accumulation of advanced glycation end products (AGEs) exerting their adverse effects via receptor of AGE (RAGE). Soluble RAGE (sRAGE) is a truncated form of RAGE functioning as an inhibitor of AGE-mediated signalling. We studied relationships between sRAGE, renal function and genetic variability in the AGER gene in diabetic subjects. Study comprised a total of 265 diabetics (type 1 or 2 or LADA) with normoalbuminuria (n = 94) or DN (n = 171). sRAGE (assessed by ELISA) was significantly higher in DN than normoalbuminuria subjects (P = 0.007) and positively correlated with age, S-urea, S-creatinine and albuminuria and AGEs (determined spectrofluorimetrically), negatively with GFR (all P < 0.05); however, multivariate regression revealed that GFR was the only independent variable associated with sRAGE (P = 0.047). sRAGE did not correspond with carrier state of risk-haplotype copies (RAGE2) (P > 0.05). In conclusion, GFR is a principal determinant of sRAGE concentration and gradual sRAGE increase in subjects with advancing impairment of renal function is paralleled by AGEs.
authors.affiliation: Department of Pathophysiology, Faculty of Medicine, Masaryk University, UKB Kamenice 5/A18, Brno, Czech Republic. kankov@med.muni.cz
authors.forename: Katerina
authors.initials: K
authors.lastname: Kanková
authors.forename: Marta
authors.initials: M
authors.lastname: Kalousová
authors.forename: Miluse
authors.initials: M
authors.lastname: Hertlová
authors.forename: Darja
authors.initials: D
authors.lastname: Krusová
authors.forename: Jindrich
authors.initials: J
authors.lastname: Olsovský
authors.forename: Tomás
authors.initials: T
authors.lastname: Zima
mesh_terms: D000368:Aged; D003430:Cross-Sectional Studies; D003928:Diabetic Nephropathies / Q000235:genetics* / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D014644:Genetic Variation; D005919:Glomerular Filtration Rate; D017127:Glycation End Products, Advanced / Q000097:blood; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics*
chemical_list: D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic