2. Academic Validation
  3. Association between the Advanced Glycosylation End Product-Specific Receptor Gene and Cardiovascular Death in Older Men

Association between the Advanced Glycosylation End Product-Specific Receptor Gene and Cardiovascular Death in Older Men

  • PLoS One. 2015 Jul 30;10(7):e0134475. doi: 10.1371/journal.pone.0134475.
Erik Biros 1,  Corey S Moran 1,  Paul E Norman 2,  Graeme J Hankey 3,  Bu B Yeap 4,  Osvaldo P Almeida 5,  Leon Flicker 6,  Richard White 7,  Rhondda Jones 1,  Jonathan Golledge 8
Affiliations

Affiliations

  • 1 Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Townsville, Australia.
  • 2 School of Surgery, University of Western Australia, Perth, Australia.
  • 3 School of Medicine and Pharmacology, University of Western Australia, Perth, Australia; Department of Neurology, Sir Charles Gairdner Hospital, Perth, Australia.
  • 4 School of Medicine and Pharmacology, University of Western Australia, Perth, Australia; Department of Endocrinology, Fremantle and Fiona Stanley Hospitals, Perth, Australia.
  • 5 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.
  • 6 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.
  • 7 Department of Neurology, The Townsville Hospital, Townsville, Australia.
  • 8 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.
PMID: 26226616 DOI: 10.1371/journal.pone.0134475
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.

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