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

Abstract

Purpose The main objective of this study was to evaluate if the À429T/C, À374T/A and 63 bp deletion polymorphisms in the RAGE gene are associated with diabetic retinopathy (DR) among Type 2 diabetic subjects in a clinicbased 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. Expectationmaximization algorithms were implemented in haplotype tests of association to examine the combined effects of À429T/C and À374T/A polymorphisms on DR. Results The allelic frequencies of À429T are 0.83 in NGT, 0.84 in DM and 0.85 in DR subjects, and that of À374T are 0.93 in NGT, 0.92 in DM and 0.88 in DR subjects. The À374 polymorphism was found to be associated with non-proliferative retinopathy when this subgroup was compared to the DM group (OR ¼ 1.814, 95% CI ¼ 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 À429T/C polymorphism and the DR phenotype. Finally, extension to a 2-SNP haplotype did not reveal any significant statistical difference between the groups (P ¼ 0.668).

The -374A Allele of the RAGE Gene As a Potential Protective Factor for Vascular Complications in Type 2 Diabetes: A Meta-Analysis

“…After review, 11 articles investigating the association between the RAGE gene -374T/A polymorphism and vascular complications in T2DM met the inclusion criteria (Hudson et al 2001;Globocnik Petrovic et al 2003;JiXiong et al 2003;Kirbis et al 2004;dos Santos et al 2005;Kankova et al 2005;Lindholm et al 2006;Ramprasad et al 2007;Lindholm et al 2008;Lu et al 2008;Peng et al 2009). These articles were published between 2001 and 2009.…”

Novel Genetic Actors of Diabetes-Associated Microvascular Complications: Retinopathy, Kidney Disease and Neuropathy

“…between the -374 T/A polymorphism and sightthreatening DR [37,38]. Two meta-analysis performed in Caucasian and Asian populations, however, did not find a significant association between RAGE polymorphisms (-374A, Gly82Ser, and -429T/C) and DR [39,40].…”

A game changer for eye care for diabetes

“…AGE formation damages cells by impairing the function of many proteins including extracellular structural proteins such as collagen 170 . AGEs also alter cellular function by binding to receptors (RAGE) 656 , producing a cascade of cellular signalling events leading to protein kinase C activation 170 . People with diabetes have markedly higher serum AGE levels than those without diabetes 171 .…”

“…People with diabetes have markedly higher serum AGE levels than those without diabetes 171 . RAGE gene promoter polymorphisms are associated with DR 656 , and interactions between AGEs and RAGE induce VEGF production 626 . There is thus evidence for a pathogenic role of AGEs in the initiation and progression of DR 655;657 .…”