The RAGE Gly82Ser polymorphism is not associated with cardiovascular disease in the Framingham offspring study

Marion A. Hofmann, Qiong Yang, Evis Harja, Prashant Kedia, Peter K. Gregersen, L. Adrienne Cupples, Ann Marie Schmidt, Barry I. Hudson

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

The receptor for advanced glycation end-products (RAGE) is expressed to enhance degrees in human atherosclerotic plaques and co-localizes with inflammatory and pro-oxidant mediators in the vulnerable regions of the plaque. Previous studies highlighted a number of variants in the gene encoding the receptor, including a Gly to Ser substitution at amino acid 82 within the ligand-binding domain of RAGE. The Ser82 allele enhanced ligand-binding affinity and increased ligand-stimulated generation of inflammatory mediators in transfected cells and human monocytes compared to the common RAGE Gly82 allele. Thus it was logical to test the hypothesis that increased prevalence of the Gly82Ser polymorphism was associated with cardiovascular events in the Framingham offspring study (n = 1632). Our analyses revealed that the Gly82Ser RAGE polymorphism did not demonstrate any association with the incidence of cardiovascular disease in diabetic or non-diabetic subjects (Gly82 96%, Ser82 4%). Analysis of specific manifestations of cardiovascular disease, including coronary heart disease (CHD), cardiovascular disease (CVD), myocardial infarction (MI) and ischemic disease (ISD) revealed no association with RAGE genotype. Further studies are required on other more prevalent genetic variants of RAGE and cardiovascular disease.

Original languageEnglish (US)
Pages (from-to)301-305
Number of pages5
JournalAtherosclerosis
Volume182
Issue number2
DOIs
StatePublished - Oct 1 2005
Externally publishedYes

Keywords

  • Advanced glycation end-products
  • Cardiovascular diseases
  • Cohort studies
  • Coronary disease
  • Diabetes mellitus
  • Immunologic receptors
  • Myocardial infarction
  • Polymorphism (genetics)
  • Population genetics

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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