title: Association of the RAGE G82S polymorphism with Alzheimer's disease.
abstract: The receptor for advanced glycation end-products (RAGE) has been implicated in several pathophysiological processes relevant to Alzheimer's disease (AD), including transport and synaptotoxicity of AD-associated amyloid beta (Abeta) peptides. A recent Chinese study (Li et al. in J Neural Transm 117:97-104, 2010) suggested an association between the 82S allele of the functional single nucleotide polymorphism (SNP) G82S (rs2070600) in the RAGE-encoding gene AGER and risk of AD. The present study aimed to investigate associations between AGER, AD diagnosis, cognitive scores and cerebrospinal fluid AD biomarkers in a European cohort of 316 neurochemically verified AD cases and 579 controls. Aside from G82S, three additional tag SNPs were analyzed to cover the common genetic variation in AGER. The 82S allele was associated with increased risk of AD (P (c) = 0.04, OR = 2.0, 95% CI 1.2-3.4). There was no genetic interaction between AGER 82S and APOE epsilon4 in producing increased risk of AD (P = 0.4), and none of the AGER SNPs showed association with Abeta(42), T-tau, P-tau(181) or mini-mental state examination scores. The data speak for a weak, but significant effect of AGER on risk of AD.
authors.affiliation: Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, 432, 405 30, Gothenburg, Sweden. jonny.daborg@physiol.gu.se
authors.forename: Jonny
authors.initials: J
authors.lastname: Daborg
authors.forename: Malin
authors.initials: M
authors.lastname: von Otter
authors.forename: Annica
authors.initials: A
authors.lastname: Sjölander
authors.forename: Staffan
authors.initials: S
authors.lastname: Nilsson
authors.forename: Lennart
authors.initials: L
authors.lastname: Minthon
authors.forename: Deborah R
authors.initials: DR
authors.lastname: Gustafson
authors.forename: Ingmar
authors.initials: I
authors.lastname: Skoog
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000235:genetics* / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D053327:Apolipoprotein E4 / Q000235:genetics; D015415:Biomarkers / Q000134:cerebrospinal fluid; D016022:Case-Control Studies; D015331:Cohort Studies; D005060:Europe; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D010766:Phosphorylation; D020641:Polymorphism, Single Nucleotide; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics*; D012306:Risk; D017422:Sequence Analysis, DNA; D016875:tau Proteins / Q000134:cerebrospinal fluid / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D015415:Biomarkers; C054369:MAPT protein, human; D010446:Peptide Fragments; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C075222:amyloid beta-protein (1-42); D016875:tau Proteins