Association between the advanced glycosylation end product-specific receptor gene and cardiovascular death in older men

Biros, Erik, Moran, Corey S., Norman, Paul E., Hankey, Graeme J., Yeap, Bu B., Almeida, Osvaldo P., Flicker, Leon, White, Richard, Jones, Rhondda, and Golledge, Jonathan (2015) Association between the advanced glycosylation end product-specific receptor gene and cardiovascular death in older men. PLoS ONE, 10 (7). e0134475. pp. 1-12.

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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.

Item ID: 41772
Item Type: Article (Research - C1)
ISSN: 1932-6203
Additional Information:

Copyright: © 2015 Biros et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Funders: Townsville Private Practice Trust Fund (TPPTF), National Health and Medical Research Council of Australia (NHMRC), National Heart Foundation of Australia (NHF), Health and Medical Research Office, Queensland Government
Projects and Grants: TPPTF RG04213, NHMRC 1022752, NHMRC 1021416, NHMRC 1020955, NHMRC 1003707, NHMRC 1000967, NHMRC 1019921
Date Deposited: 08 Dec 2015 17:40
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1102 Cardiovascular Medicine and Haematology > 110201 Cardiology (incl Cardiovascular Diseases) @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920103 Cardiovascular System and Diseases @ 100%
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