The -374A allele of the RAGE gene as a potential protective factor for vascular complications in type 2 diabetes: a meta-analysis

Tohoku J Exp Med. 2010 Apr;220(4):291-7. doi: 10.1620/tjem.220.291.


The receptor for advanced glycation end products (RAGE) is a multi-ligand member of the immunoglobulin superfamily and may be involved in the development of diabetic vascular complications. The -374T/A polymorphism in the RAGE gene promoter has been suggested to affect gene transcription. However, the studies on the association between the -374T/A polymorphism and vascular complications in type 2 diabetes mellitus (T2DM) have rendered conflicting results. To shed light on these inconclusive findings, a meta-analysis of all eligible studies concerning this polymorphism was conducted. The PubMed and EMBASE databases were searched for relevant articles up to January 2010. Data on genotypes, allele frequencies and number of cases and controls were extracted. A pooled estimate of the genetic association, the heterogeneity between studies, the sensitivity for HWE (exclusion of studies not in Hardy-Weinberg equilibrium), and the publication bias were investigated. Nine articles with 3,799 cases and 4,899 controls were enrolled in the meta-analysis. The main analysis indicated significant heterogeneity and no association for the allele contrast [random effects odds ratio (RE OR) = 0.92 (0.83 approximately 1.02)]. However, sensitivity analysis for HWE diminished the heterogeneity and showed a marginal association [fixed effects OR = 0.92 (0.86 approximately 0.99)]. The comparison of AA genotype with TA+TT genotypes revealed significant results overall [RE OR = 0.70 (0.57 approximately 0.86)]. Subgroup analyses in Caucasians and macrovascualr disease also produced significant association. In conclusion, the -374A allele of the RAGE gene might be a protective factor for vascular complications in T2DM, especially in Caucasians and macrovascular disease.

Publication types

  • Meta-Analysis

MeSH terms

  • Alleles
  • Blood Vessels / pathology
  • Blood Vessels / physiopathology
  • Databases, Factual
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / pathology
  • Diabetes Mellitus, Type 2 / physiopathology
  • Diabetic Angiopathies / genetics*
  • Genetic Predisposition to Disease
  • Humans
  • Odds Ratio
  • Polymorphism, Genetic
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic / genetics*
  • Risk Factors


  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic