RAGE (receptor for advanced glycation endproducts) polymorphisms in Alzheimer Disease

Abstract

The Receptor for Advanced Glycation Endproducts (RAGE), a multi-ligand receptor of the immunoglobulin superfamily, functions as a signal-transducing cell surface acceptor for Afbeta(amyloid beta protein). The expression of RAGE in several cell types (neurons, glial cells, and endothelial cells) and its presence at multiple sites highlights the importance of RAGE in cellular responses. The RAGE gene is located on chromosome 6p21.3, a region for which genetic linkage to AD (Alzheimer disease) has been reported. Keshen Li et al (2009) have studied the association of AD with a functional single-nucleotide polymorphism (SNP) of RAGE gene (G82S; rs2070600), a SNP associated with increased ligand affinity. Analysis of a Chinese cohort of patients showed a higher prevalence of the RAGE 82S allele and the GS+SS genotype. Further stratification analysis of patients revealed that this association was significant in early onset AD stratum. In this study, we investigated two promoter polymorphisms of the RAGE gene, -374 T/A and -429 C/T (implicated in expression of the gene) in 60 Italian AD patients and healthy controls. The analysis of these polymorphisms did not show any significant differences of allelic and genotypic frequencies between the two groups. In our study, we have not yet taken into account the G82S polymorphism because this polymorphism is monomorphic in our population. Furthermore, the contrasting results obtained by us as compared to the data from the Chinese population could reflect the fact that the patients in our cohort had late onset AD.