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BioMed Research International
Volume 2013 (2013), Article ID 318686, 9 pages
Research Article

Association of Toll-Like Receptor 4 Polymorphisms with Diabetic Foot Ulcers and Application of Artificial Neural Network in DFU Risk Assessment in Type 2 Diabetes Patients

1Department of Molecular & Human Genetics, Banaras Hindu University, Varanasi 221005, India
2Department of Mining Engineering, Indian Institute of Technology, Banaras Hindu University, Varanasi 221005, India
3Department of Endocrinology and Metabolism, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India
4Department of General Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India

Received 23 April 2013; Revised 16 June 2013; Accepted 17 June 2013

Academic Editor: Thomas Liehr

Copyright © 2013 Kanhaiya Singh et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The Toll-Like receptor 4 (TLR4) plays an important role in immunity, tissue repair, and regeneration. The objective of the present work was to evaluate the association of TLR4 single nucleotide polymorphisms (SNPs) rs4986790, rs4986791, rs11536858 (merged into rs10759931), rs1927911, and rs1927914 with increased diabetic foot ulcer (DFU) risk in patients with type 2 diabetes mellitus (T2DM). PCR-RFLP was used for genotyping TLR4 SNPs in 125 T2DM patients with DFU and 130 controls. The haplotypes and linkage disequilibrium between the SNPs were determined using Haploview software. Multivariate linear regression (MLR) and artificial neural network (ANN) modeling was done to observe their predictability for the risk of DFU in T2DM patients. Risk genotypes of all SNPs except rs1927914 were significantly associated with DFU. Haplotype ACATC ( value = ) showed strong association with DFU risk. Two haplotypes ATATC ( value = 0.0119) and ATGTT ( value = 0.0087) were found to be protective against DFU. In conclusion TLR4 SNPs and their haplotypes may increase the risk of impairment of wound healing in T2DM patients. ANN model (83%) is found to be better than the MLR model (76%) and can be used as a tool for the DFU risk assessment in T2DM patients.