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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.
Gene 2013; 526(2):325-30GENE

Abstract

BACKGROUND AND AIMS

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).

OBJECTIVES

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).

CONCLUSION

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+Show Affiliations

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.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23721855

Citation

Bansal, Savita, et al. "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." Gene, vol. 526, no. 2, 2013, pp. 325-30.
Bansal S, Chawla D, Banerjee BD, et al. 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. Gene. 2013;526(2):325-30.
Bansal, S., Chawla, D., Banerjee, B. D., Madhu, S. V., & Tripathi, A. K. (2013). 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. Gene, 526(2), pp. 325-30. doi:10.1016/j.gene.2013.05.013.
Bansal S, et al. 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. Gene. 2013 Sep 10;526(2):325-30. PubMed PMID: 23721855.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Bansal,Savita, AU - Chawla,Diwesh, AU - Banerjee,Basu Dev, AU - Madhu,Sri Venkata, AU - Tripathi,Ashok Kumar, Y1 - 2013/05/27/ PY - 2013/01/31/received PY - 2013/05/01/revised PY - 2013/05/06/accepted PY - 2013/6/1/entrez PY - 2013/6/1/pubmed PY - 2013/10/19/medline KW - AGEs KW - Advanced glycation end products KW - CVD KW - Cardiovascular disease KW - DM-MVC KW - Diabetes mellitus with macro-vascular complications KW - Glycated hemoglobin KW - HLD KW - HbA(1C) KW - High density lipoprotein KW - LDL KW - Low density lipoprotein KW - MVC KW - Macro-vascular complications KW - PON1 KW - Paraoxonase KW - Paraoxonase 1 KW - RAGE KW - Receptor for advanced glycation end products KW - SNPs KW - Single nucleotide polymorphism KW - T2DM KW - Type 2 diabetes mellitus SP - 325 EP - 30 JF - Gene JO - Gene VL - 526 IS - 2 N2 - BACKGROUND AND AIMS: 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). OBJECTIVES: 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). CONCLUSION: 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. SN - 1879-0038 UR - https://www.unboundmedicine.com/medline/citation/23721855/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-1119(13)00649-5 DB - PRIME DP - Unbound Medicine ER -