The functional -374 T/A RAGE gene polymorphism is associated with proteinuria and cardiovascular disease in type 1 diabetic patients

Kim Pettersson-Fernholm, Carol Forsblom, Barry I. Hudson, Markus Perola, Peter J. Grant, Per Henrik Groop

Research output: Contribution to journalArticle

114 Scopus citations

Abstract

The hyperglycemic milieu in diabetes results in the formation of advanced glycation end products (AGEs) that predominantly act through specific receptors, particularly the receptor for AGEs(RAGE). Two functional polymorphisms in the promoter of the RAGE gene (-429 T/C and -374 T/A) and one in the AGE binding domain in exon 3 (G82S) were studied in 996 Finnish type 1 diabetic patients. In patients with poor metabolic control (HbA1c, > 9.5%), the AA genotype of the -374 T/A polymorphism was more common in those with a normal albumin excretion rate than in those with proteinuria (30 vs. 10%, P = 0.01), We observed less coronary heart disease (6 vs. 14%, P < 0.05), acute myocardial infarction (2 vs. 14%, P = 0.01), and peripheral vascular disease (2 vs. 14%, P < 0.05) in patients with the AA genotype of the -374 T/A polymorphism than in those with the TT + TA genotype, Thus, the association between the RAGE -374 T/A homozygous AA genotype and cardiovascular disease as well as albumin excretion in type 1 diabetic patients with poor metabolic control suggests a gene-environment interaction in the development of diabetic nephropathy and cardiovascular complications.

Original languageEnglish (US)
Pages (from-to)891-894
Number of pages4
JournalDiabetes
Volume52
Issue number3
DOIs
StatePublished - Mar 1 2003
Externally publishedYes

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Keywords

  • AER, albumin excretion rate
  • AGE, advanced glycation end product
  • AM1, acute myocardial infarction
  • CHD, coronary heart disease
  • CVD, cardiovascular disease
  • ESRD, end-stage renal disease
  • PVD, peripheral vascular disease

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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