Identification of polymorphisms in the receptor for advanced glycation end products (RAGE) gene: prevalence in type 2 diabetes and ethnic groups.

RAGE and arthritis: the G82S polymorphism amplifies the inflammatory response

“…4 Recent studies have highlighted the possibility that polymorphisms within key domains of RAGE may influence its function, so that under conditions of increased ligand accumulation, individuals may be predisposed to heightened inflammatory responses. 8,9 Importantly, a polymorphism of the RAGE gene has been identified within the V-type immunoglobulin domain in the extracellular region of the receptor, consisting of a glycine to serine change at position 82. 8 In previous studies, we found that the ligands of RAGE, including S100/calgranulins, engage the V-domain of the receptor and activate signal transduction pathways, thereby modulating gene expression.…”

“…8,9 Importantly, a polymorphism of the RAGE gene has been identified within the V-type immunoglobulin domain in the extracellular region of the receptor, consisting of a glycine to serine change at position 82. 8 In previous studies, we found that the ligands of RAGE, including S100/calgranulins, engage the V-domain of the receptor and activate signal transduction pathways, thereby modulating gene expression. 1,[10][11][12][13][14] These considerations led us to hypothesize that activation of RAGE contributed to proinflammatory responses in immune/inflammatory disorders such as RA, and that RAGE 82S might further enhance generation of inflammatory mediators linked to chronic tissue injury.…”

Effects of Novel Polymorphisms in the RAGE Gene on Transcriptional Regulation and Their Association With Diabetic Retinopathy

“…PCR fragments (RAGECAT) were amplified using Expand High Fidelity PCR system as before with a extension of 10 min to A-tail the PCR product to enable cloning into the pCR2.1 TOPO vector (Invitrogen). Five RAGECAT constructs were generated: a wild type for all polymorphisms, a C at -429, an A at -374, a 63-bp deletion from -407 to -345, and a T at ϩ20, as described by Hudson et al (17). Five clones for each genotype were mini-prep purified as before and sequenced using M13 primers (M13F 5Ј GTAAAACGACGGCCAG 3Ј M13R 5Ј CAGGAAA-CAGCTATGAC 3Ј) by an automated method, as previously described.…”

How RAGE turns in rage

“…These results demonstrate a significant functional difference in binding, signalling and gene expression between the allelic RAGE 82S and 82G receptors. In a previous study Hudson et al 12 reported on the functional relevance of RAGE promoter polymorphisms at position −429, −374 and −63, suggesting that also genetically determined differences at the level of RAGE production may exist. 12 Together these data suggest that polymorphism within the RAGE gene affect RAGE signalling and may influence disease susceptibility and/or outcome.…”

“…Most interestingly, the search for heterogeneity within the RAGE gene uncovered several polymorphisms. 12,13 However, since polymorphic genes within the MHC display a high degree of linkage disequilibrium, disease-associations found do not necessarily direct to a functional variation but could well be the consequence of a nearby diseasecausing allele. In fact, most disease-associated polymorphisms are functionally inert or lack information on the functional relevance.…”