Soluble RAGE, diabetic nephropathy and genetic variability in the AGER gene
Language English Country England, Great Britain Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Diabetic Nephropathies genetics physiopathology MeSH
- Enzyme-Linked Immunosorbent Assay MeSH
- Genetic Variation * MeSH
- Haplotypes MeSH
- Glomerular Filtration Rate MeSH
- Middle Aged MeSH
- Humans MeSH
- Glycation End Products, Advanced blood MeSH
- Cross-Sectional Studies MeSH
- Receptor for Advanced Glycation End Products MeSH
- Receptors, Immunologic genetics MeSH
- Aged MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Glycation End Products, Advanced MeSH
- Receptor for Advanced Glycation End Products MeSH
- Receptors, Immunologic MeSH
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.
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