Rage gene promoter polymorphisms and diabetic retinopathy in a clinic-based population from South India

Eye (Lond). 2007 Mar;21(3):395-401. doi: 10.1038/sj.eye.6702239. Epub 2006 Jan 27.

Abstract

Purpose: The main objective of this study was to evaluate if the -429T/C, -374T/A and 63 bp deletion polymorphisms in the RAGE gene are associated with diabetic retinopathy (DR) among Type 2 diabetic subjects in a clinic-based population from South India.

Methods: We screened 149 normal glucose tolerant subjects (NGT), 189 Type 2 diabetes subjects without retinopathy (DM) and 190 subjects with DR for these polymorphisms using the PCR-RFLP method. DR was diagnosed by grading color fundus photography. Logistic regression models were used to evaluate the association of individual polymorphisms with DR. Expectation-maximization algorithms were implemented in haplotype tests of association to examine the combined effects of -429T/C and -374T/A polymorphisms on DR.

Results: The allelic frequencies of -429T are 0.83 in NGT, 0.84 in DM and 0.85 in DR subjects, and that of -374T are 0.93 in NGT, 0.92 in DM and 0.88 in DR subjects. The -374 polymorphism was found to be associated with non-proliferative retinopathy when this subgroup was compared to the DM group (OR=1.814, 95% CI=1.005-3.273). However, this association was not obvious when both the subphenotypes of DR (the nonproliferative and proliferative DR groups) were studied jointly. We found no evidence for associations between the -429T/C polymorphism and the DR phenotype. Finally, extension to a 2-SNP haplotype did not reveal any significant statistical difference between the groups (P=0.668).

Conclusion: In this study, we found a modest association with the -374T/A polymorphism in the nonproliferative DR subgroup.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetic Retinopathy / blood
  • Diabetic Retinopathy / epidemiology
  • Diabetic Retinopathy / genetics*
  • Female
  • Gene Deletion
  • Gene Frequency / genetics
  • Haplotypes
  • Humans
  • India / epidemiology
  • Male
  • Middle Aged
  • Phenotype
  • Polymorphism, Genetic / genetics*
  • Polymorphism, Single Nucleotide / genetics
  • Promoter Regions, Genetic / genetics
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic / genetics*

Substances

  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic