Polymorphisms in the RAGE gene influence susceptibility to diabetes-associated microvascular dermatoses in NIDDM

J Diabetes Complications. 2001 Jul-Aug;15(4):185-92. doi: 10.1016/s1056-8727(00)00135-5.


To examine genetic polymorphism in the complete sequence of the Receptor of Advanced Glycation End products (RAGE) gene and its possible associations with diabetes-associated microvascular dermatoses (DAMD). Further, to analyze the distribution of individual genotype combinations on the particular polymorphic loci in the RAGE gene. A part of the RAGE gene spanning a region from -4 to 3334 bp was analyzed on a set of 45 subjects with non-insulin dependent diabetes mellitus (NIDDM) and parallel DAMD by means of PCR with subsequent heteroduplex and single-strand conformation polymorphism (SSCP) analyses. Allele frequencies and genotype combinations of novel common polymorphisms were determined in an associations study comprising four groups of subjects (n=390). Fourteen novel polymorphisms (R77C, V89V, 718G/T, 1704G/T, 1727A1728ins, H305Q, S307C, 2117A/G, 2184A/G, 2245G/A, 2249A/G, 2741G/A, and 3089ACdel) and one described previously (G82S) were identified. Significant association with microvascular dermatoses (MD) irrespective of NIDDM were found for exon mutation 82S (P= .004, after a correction for the number of comparisons P(corr) < .05) and marginally significant for intron variant 1704T (P= .032, P(corr)> .05). Calculated odds ratios for 82S and 1704T were 4.73 (95% CI, 1.51 to 14.77) and 1.73 (95% CI, 0.93 to 3.22), respectively. Certain individual genotype combinations of G82S, 1704G/T, and 2184A/G were significantly associated with the presence of MD (P= .00647) both in diabetic and non-diabetic study populations. The two novel polymorphisms (1704G/T and 2184A/G) together with the G82S were shown to influence the susceptibility to MD independent of diabetes itself.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amino Acid Substitution
  • Czech Republic
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Diabetic Angiopathies / genetics*
  • Exons
  • Female
  • Genetic Predisposition to Disease*
  • Glycation End Products, Advanced / metabolism
  • Humans
  • Male
  • Microcirculation / physiopathology*
  • Middle Aged
  • Mutation, Missense
  • Point Mutation
  • Polymorphism, Genetic*
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic / chemistry
  • Receptors, Immunologic / genetics*
  • Sequence Deletion
  • Skin / blood supply
  • Skin Diseases / complications
  • Skin Diseases / genetics*
  • Whites


  • Glycation End Products, Advanced
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic