7th Indo Global Diabetes Summit and Medicare Expo
Central Research Laboratory
Title: Genetic Variant of RAGE gene and its Enhanced Expression: Risk factor For Vascular Complications In Type 2 Diabetes Mellitus
Biography: Diwesh Chawla
BACKGROUND AND AIM: Advanced glycation end products (AGEs) are formed as a result of spontaneous non-enzymatic glycosylation of biomolecules, like proteins, lipids, nucleic acids. Interaction of AGEs with its receptor RAGE induces signal transduction that culminates in vascular complications, the major cause of morbidity and mortality in diabetic subjects. Some functional polymorphism of RAGE gene show differential activity of this receptor and therefore may be associated with the development of vascular complications in diabetic patients. In the present study we estimated blood level of AGEs and investigated the association of expression of RAGE gene and its genetic variants namely -374T/A and -429T/C in the promoter region and Gly82Ser polymorphism in the exon 3 region with vascular complications in T2DM patients.
METHODS: We screened 820 subjects which includes 200 healthy controls, 200 type 2 diabetes mellitus (T2DM) subjects without any vascular complications (DM), 220 T2DM subjects with microvascular complications (DM-Micro) and 200 T2DM subjects with macrovascular complications (DM-Macro) for -374 T/A, -429 T/C and Gly82Ser polymorphisms of RAGE gene. DNA isolated from the enrolled subjects were genotyped by PCR-RFLP. RAGE expression was determined by quantitative real-time PCR. Serum AGEs was estimated by spectrofluorometry
RESULTS: Serum AGEs level was significantly higher in diabetic patients having vascular complications as compared to T2DM without complications (p < 0.01). Mutant variant of -429T/C and Gly82Ser RAGE polymorphism was about three times more prone to develop macrovascular and microvascular complications respectively in T2DM subjects while -374A allele showed reduced risk towards the development of macrovascular complications (OR = 0.57, p = 0.006). Further, haplotype analysis revealed that CTG haplotype was significantly associated with the development of macrovascular complications while haplotype TAG was observed to be significantly protective towards development of macrovascular complications in T2DM subjects. The expression of RAGE correlated significantly with the genotypic variation of the RAGE gene.
CONCLUSION: Mutant genotypes of RAGE gene and enhanced formation and accumulation of AGEs under hyperglycemic conditions enhance RAGE expression in diabetic patients causing increased AGE-RAGE interaction, may be considered as risk factor for vascular complications in North Indian T2DM patients.