Association of RAGE gene polymorphism with vascular complications in Indian type 2 diabetes mellitus patients Ashok Kumar Tripathi a, *, Diwesh Chawla a , Savita Bansal a , Basu Dev Banerjee a , Sri Venkata Madhu b , Om Prakash Kalra b a 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 b Department of Medicine, University College of Medical Sciences (University of Delhi) and G.T.B. Hospital, Dilshad Garden, Delhi 110095, India 1. Introduction Hyperglycemia associated with diabetes mellitus stimulate non-enzymatic glycation and oxidation of proteins and lipids leading to enhanced formation of advanced glycation end products (AGEs) [1,2]. High levels of AGEs are reported in diabetes mellitus (DM) patients compared to healthy indivi- duals. The formation and accumulation of AGEs constitute the characteristic feature in diabetes [3–5]. There is growing evidence that production and accumulation of AGEs is involved in the initiation and development of micro and d i a b e t e s r e s e a r c h a n d c l i n i c a l p r a c t i c e 1 0 3 ( 2 0 1 4 ) 4 7 4 – 4 8 1 a r t i c l e i n f o Article history: Received 11 July 2013 Received in revised form 19 September 2013 Accepted 18 December 2013 Available online 25 December 2013 Keywords: Type 2 diabetes mellitus RAGE gene Polymorphism Vascular complications a b s t r a c t Aims: The study was designed to evaluate the association of À374T/A and À429T/C poly- morphism in the promoter region and Gly82Ser polymorphism in exon 3 region of RAGE gene with diabetic vascular complications in Indian population. Methods: We screened 603 subjects which includes 176 healthy controls, 140 type 2 diabetes mellitus (T2DM) subjects without any vascular complications (DM), 152 T2DM subjects with microvascular complications (DM-micro) and 135 T2DM subjects with macrovascular com- plications (DM-macro) for À374T/A, À429T/C and Gly82Ser polymorphisms of RAGE gene. DNA isolated from the enrolled subjects were genotyped by PCR-RFLP. Logistic regression analysis was used to evaluate the association of single nucleotide polymorphisms (SNPs). Results: The À429 T/C and Gly82Ser RAGE polymorphisms were found to be significantly associated with the development of macrovascular and microvascular complications, respectively, in T2DM subjects while À374A allele showed reduced risk towards the devel- opment of macrovascular complications. Further, À429T/C, À374T/A and Gly82Ser haplo- type analysis revealed association of CTG haplotype with development of macrovascular complications while haplotype TAG was observed to be significantly protective towards development of macrovascular complications in T2DM subjects (OR = 0.617, p = 0.0202). Conclusions: Our data indicates significant association of RAGE SNPs and haplotypes with vascular complications in North Indian T2DM subjects. # 2013 Elsevier Ireland Ltd. All rights reserved. * Corresponding author. Tel.: +91 11 22582972 74x5210/+91 9811259019 (mob); fax: +91 11 22590495. E-mail addresses: aktripathiucms@gmail.com (A.K. Tripathi), diweshchawla@yahoo.co.in (D. Chawla), bansalsavita_1916@yahoo.com (S. Bansal), banerjeebd@hotmail.com (B.D. Banerjee), drsvmadhu@gmail.com (S.V. Madhu), opkalra1@yahoo.com (O.P. Kalra). Contents available at ScienceDirect Diabetes Research and Clinical Practice journal homepage: www.elsevier.com/locate/diabres 0168-8227/$ – see front matter # 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.diabres.2013.12.004