title: Association of RAGE gene polymorphism with circulating AGEs level and paraoxonase activity in relation to macro-vascular complications in Indian type 2 diabetes mellitus patients.
abstract: OBJECTIVE
  Sustained interaction of advanced glycation end products (AGEs) with their receptor RAGE and subsequent signaling plays an important role in the development of diabetic complications. Genetic variation of RAGE gene may be associated with the development of vascular complications in type 2 diabetes mellitus (T2DM).
  
  
  OBJECTIVE
  The present study aimed to explore the possible association of RAGE gene polymorphisms namely -374T/A, -429T/C and G82S with serum level of AGEs, paraoxonase (PON1) activity and macro-vascular complications (MVC) in Indian type 2 diabetes mellitus patients (T2DM).
  
  
  METHODS
  A total of 265 diabetic patients, including DM without any complications (n=135), DM-MVC (n=130) and 171 healthy individuals were enrolled. Genotyping of RAGE variants were assessed by polymerase chain reaction-restriction fragment length polymorphism. Serum AGEs were estimated by ELISA and fluorometrically. and PON1 activity was assessed spectrophotometrically.
  
  
  RESULTS
  Of the three examined SNPs, association of -429T/C polymorphism with MVC in T2DM was observed (OR=3.001, p=0.001) in the dominant model. Allele 'A' of -374T/A polymorphism seems to confer better cardiac outcome in T2DM. Patients carrying C allele (-429T/C) and S allele (G82S) had significantly higher AGEs levels. -429T/C polymorphism was also found to be associated with low PON1 activity. Interaction analysis revealed that the risk of development of MVC was higher in T2DM patients carrying both a CC genotype of -429T/C polymorphism and a higher level of AGEs (OR=1.343, p=0.040).
  
  
  CONCLUSIONS
  RAGE gene polymorphism has a significant effect on AGEs level and PON1 activity in diabetic subjects compared to healthy individuals. Diabetic patients with a CC genotype of -429T/C are prone to develop MVC, more so if AGEs levels are high and PON1 activity is low.
authors.affiliation: Biochemistry and Immunology Laboratory, Department of Biochemistry, University College of Medical Sciences, University of Delhi, and G.T.B. Hospital, Dilshad Garden, Delhi 110095, India. bansalsavita_1916@yahoo.com
authors.forename: Savita
authors.initials: S
authors.lastname: Bansal
authors.forename: Diwesh
authors.initials: D
authors.lastname: Chawla
authors.forename: Basu Dev
authors.initials: BD
authors.lastname: Banerjee
authors.forename: Sri Venkata
authors.initials: SV
authors.lastname: Madhu
authors.forename: Ashok Kumar
authors.initials: AK
authors.lastname: Tripathi
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D043303:Aryldialkylphosphatase / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000235:genetics*; D003925:Diabetic Angiopathies / Q000097:blood* / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D017127:Glycation End Products, Advanced / Q000097:blood*; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D000067759:Receptor for Advanced Glycation End Products / Q000235:genetics*
chemical_list: D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human
keywords: AGEs; Advanced glycation end products; CVD; Cardiovascular disease; DM-MVC; Diabetes mellitus with macro-vascular complications; Glycated hemoglobin; HLD; HbA(1C); High density lipoprotein; LDL; Low density lipoprotein; MVC; Macro-vascular complications; PON1; Paraoxonase; Paraoxonase 1; RAGE; Receptor for advanced glycation end products; SNPs; Single nucleotide polymorphism; T2DM; Type 2 diabetes mellitus