Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

The Gly82Ser polymorphism in the receptor for advanced glycation endproducts increases the risk for coronary events in the general population

Grauen Larsen, Helena LU ; Sun, Jiangming LU orcid ; Sjögren, Marketa LU ; Borné, Yan LU ; Engström, Gunnar LU ; Nilsson, Peter LU ; Orho-Melander, Marju LU ; Goncalves, Isabel LU orcid ; Nilsson, Jan LU and Melander, Olle LU orcid , et al. (2024) In Scientific Reports 14(1).
Abstract

The receptor for advanced glycation endproducts (RAGE) has pro-inflammatory and pro-atherogenic effects. Low plasma levels of soluble RAGE (sRAGE), a decoy receptor for RAGE ligands, have been associated with increased risk for major adverse coronary events (MACE) in the general population. We performed a genome-wide association study to identify genetic determinants of plasma sRAGE in 4338 individuals from the cardiovascular arm of the Malmö Diet and Cancer study (MDC-CV). Further, we explored the associations between these genetic variants, incident first-time MACE and mortality in 24,640 unrelated individuals of European ancestry from the MDC cohort. The minor alleles of four single nucleotide polymorphisms (SNPs): rs2070600,... (More)

The receptor for advanced glycation endproducts (RAGE) has pro-inflammatory and pro-atherogenic effects. Low plasma levels of soluble RAGE (sRAGE), a decoy receptor for RAGE ligands, have been associated with increased risk for major adverse coronary events (MACE) in the general population. We performed a genome-wide association study to identify genetic determinants of plasma sRAGE in 4338 individuals from the cardiovascular arm of the Malmö Diet and Cancer study (MDC-CV). Further, we explored the associations between these genetic variants, incident first-time MACE and mortality in 24,640 unrelated individuals of European ancestry from the MDC cohort. The minor alleles of four single nucleotide polymorphisms (SNPs): rs2070600, rs204993, rs116653040, and rs7306778 were independently associated with lower plasma sRAGE. The minor T (vs. C) allele of rs2070600 was associated with increased risk for MACE [HR 1.13 95% CI (1.02–1.25), P = 0.016]. Neither SNP was associated with mortality. This is the largest study to demonstrate a link between a genetic sRAGE determinant and CV risk. Only rs2070600, which enhances RAGE function by inducing a Gly82Ser polymorphism in the ligand-binding domain, was associated with MACE. The lack of associations with incident MACE for the other sRAGE-lowering SNPs suggests that this functional RAGE modification is central for the observed relationship.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
14
issue
1
article number
11567
publisher
Nature Publishing Group
external identifiers
  • scopus:85194020956
  • pmid:38773223
ISSN
2045-2322
DOI
10.1038/s41598-024-62385-5
language
English
LU publication?
yes
id
34a34779-360f-4604-b50c-38413ef436f8
date added to LUP
2024-06-13 14:42:28
date last changed
2024-06-14 03:00:27
@article{34a34779-360f-4604-b50c-38413ef436f8,
  abstract     = {{<p>The receptor for advanced glycation endproducts (RAGE) has pro-inflammatory and pro-atherogenic effects. Low plasma levels of soluble RAGE (sRAGE), a decoy receptor for RAGE ligands, have been associated with increased risk for major adverse coronary events (MACE) in the general population. We performed a genome-wide association study to identify genetic determinants of plasma sRAGE in 4338 individuals from the cardiovascular arm of the Malmö Diet and Cancer study (MDC-CV). Further, we explored the associations between these genetic variants, incident first-time MACE and mortality in 24,640 unrelated individuals of European ancestry from the MDC cohort. The minor alleles of four single nucleotide polymorphisms (SNPs): rs2070600, rs204993, rs116653040, and rs7306778 were independently associated with lower plasma sRAGE. The minor T (vs. C) allele of rs2070600 was associated with increased risk for MACE [HR 1.13 95% CI (1.02–1.25), P = 0.016]. Neither SNP was associated with mortality. This is the largest study to demonstrate a link between a genetic sRAGE determinant and CV risk. Only rs2070600, which enhances RAGE function by inducing a Gly82Ser polymorphism in the ligand-binding domain, was associated with MACE. The lack of associations with incident MACE for the other sRAGE-lowering SNPs suggests that this functional RAGE modification is central for the observed relationship.</p>}},
  author       = {{Grauen Larsen, Helena and Sun, Jiangming and Sjögren, Marketa and Borné, Yan and Engström, Gunnar and Nilsson, Peter and Orho-Melander, Marju and Goncalves, Isabel and Nilsson, Jan and Melander, Olle and Schiopu, Alexandru}},
  issn         = {{2045-2322}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{The Gly82Ser polymorphism in the receptor for advanced glycation endproducts increases the risk for coronary events in the general population}},
  url          = {{http://dx.doi.org/10.1038/s41598-024-62385-5}},
  doi          = {{10.1038/s41598-024-62385-5}},
  volume       = {{14}},
  year         = {{2024}},
}