title: Association between the Advanced Glycosylation End Product-Specific Receptor Gene and Cardiovascular Death in Older Men.
abstract: Advanced glycosylation end product-specific receptor (AGER) signaling has been implicated in atherosclerosis. The aim of this study was to evaluate whether a common genetic variation in the AGER gene is associated with cardiovascular (CV) death. We included 1304 older men who were genotyped for rs1035798:C>T, which is a single nucleotide polymorphism (SNP) mapped to the third intron of AGER. Cox proportional hazard analysis was used to estimate the association of rs1035798:C>T with CV death. In addition we analyzed total RNA extracted from carotid atherosclerosis biopsies of 18 patients that did or did not have recent symptoms of cerebral embolization by quantitative real-time reverse transcription PCR (qRT-PCR). The minor T-allele of rs1035798:C>T was found to be associated with CV death under dominant (HR = 1.43, 95% CI: 1.01-2.02, P = 0.04) and recessive (HR = 2.05, 95% CI: 1.11-3.81, P = 0.02) models of inheritance even after adjustment for traditional cardiovascular risk factors. No association was found between rs1035798:C>T and non-CV death. qRT-PCR results suggested that median relative expression of AGER isoform 1 and isoform 6 transcripts were approximately 6- (P = 0.01) and 2-fold (P = 0.02) greater, respectively, within carotid biopsies of symptomatic compared to asymptomatic patients. These data suggest that the minor (T) allele of rs1035798:C>T represents an independent susceptibility factor for CV death. The expression of AGER isoforms is different in atheroma from patients with recent symptoms. Further studies are needed to investigate if rs1035798:C>T influences the alternative splicing of AGER.
authors.affiliation: Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Townsville, Australia.
authors.forename: Erik
authors.initials: E
authors.lastname: Biros
authors.affiliation: Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Townsville, Australia.
authors.forename: Corey S
authors.initials: CS
authors.lastname: Moran
authors.affiliation: School of Surgery, University of Western Australia, Perth, Australia.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Norman
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Perth, Australia; Department of Neurology, Sir Charles Gairdner Hospital, Perth, Australia.
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: Hankey
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Perth, Australia; Department of Endocrinology, Fremantle and Fiona Stanley Hospitals, Perth, Australia.
authors.forename: Bu B
authors.initials: BB
authors.lastname: Yeap
authors.affiliation: School of Psychiatry and Clinical Neurosciences, University of Western Australia, Perth, Australia; WA Centre for Health and Ageing, Centre for Medical Research, Perth, Australia; Department of Psychiatry, Royal Perth Hospital, Perth, Australia.
authors.forename: Osvaldo P
authors.initials: OP
authors.lastname: Almeida
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Perth, Australia; WA Centre for Health and Ageing, Centre for Medical Research, Perth, Australia; Department of Geriatric Medicine, Royal Perth Hospital, Perth, Australia.
authors.forename: Leon
authors.initials: L
authors.lastname: Flicker
authors.affiliation: Department of Neurology, The Townsville Hospital, Townsville, Australia.
authors.forename: Richard
authors.initials: R
authors.lastname: White
authors.affiliation: Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Townsville, Australia.
authors.forename: Rhondda
authors.initials: R
authors.lastname: Jones
authors.affiliation: Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Townsville, Australia; Department of Vascular and Endovascular Surgery, The Townsville Hospital, Townsville, Australia.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Golledge
mesh_terms: D002318:Cardiovascular Diseases / Q000235:genetics* / Q000401:mortality*; D005838:Genotype; D006801:Humans; D008297:Male; D016016:Proportional Hazards Models; D000067759:Receptor for Advanced Glycation End Products / Q000235:genetics*; D016019:Survival Analysis
chemical_list: C000593871:AGER protein, human; D000067759:Receptor for Advanced Glycation End Products