Association of Variant rs7903146 (C/T) Single Nucleotide Polymorphism of TCF7L2 Gene With Impairment in Wound Healing Among North Indian Type 2 Diabetes Population

The variants of transcription factor 7-like 2 (TCF7L2) gene have been shown to be associated with type 2 diabetes mellitus (T2DM) and its several secondary complications. Here, we aimed to examine the possible role of one of the common variant of this gene, rs7903146 (C/T), with impairment of wound healing in cases with T2DM. A total of 750 individuals, including 322 patients with T2DM and 120 patients with diabetic foot ulcers (DFUs) and 308 controls, were analyzed for rs7903146 variant of the TCF7L2 gene. Genotyping was done by polymerase chain reaction–restriction fragment length polymorphism. For rs7903146 variant, TT genotype frequency in patients with DFU was 10.8% and in controls was 5.2%. Risk genotype (TT) frequencies showed statistically significant difference between the DFU patients versus non-DM control group (odds ratio = 2.44, P = .037, 95% confidence interval = 1.05-5.64) compared with nonrisk genotype (CC + CT). In the present study, a positive significant association between DFU and the TT genotype of rs7903146 (C/T) variant of TCF7L2 gene was found.

[1]  V. Mohan,et al.  The rs12255372(G/T) and rs7903146(C/T) polymorphisms of the TCF7L2 gene are associated with type 2 diabetes mellitus in Asian Indians. , 2007, Metabolism: clinical and experimental.

[2]  W D Plummer,et al.  Power and sample size calculations for studies involving linear regression. , 1998, Controlled clinical trials.

[3]  B. Ramakrishna,et al.  Heat‐shock protein 70 gene polymorphism is associated with the severity of diabetic foot ulcer and the outcome of surgical treatment , 2009, The British journal of surgery.

[4]  T. Jin,et al.  TCF-4 Mediates Cell Type-specific Regulation of Proglucagon Gene Expression by β-Catenin and Glycogen Synthase Kinase-3β* , 2005, Journal of Biological Chemistry.

[5]  C. Joo,et al.  Wnt-7a Up-regulates Matrix Metalloproteinase-12 Expression and Promotes Cell Proliferation in Corneal Epithelial Cells during Wound Healing* , 2005, Journal of Biological Chemistry.

[6]  Shirley A. Miller,et al.  A simple salting out procedure for extracting DNA from human nucleated cells. , 1988, Nucleic acids research.

[7]  G. Reaven Role of Insulin Resistance in Human Disease , 1988, Diabetes.

[8]  M. Fowler Microvascular and Macrovascular Complications of Diabetes , 2008, Clinical Diabetes.

[9]  Peter Almgren,et al.  Mechanisms by which common variants in the TCF7L2 gene increase risk of type 2 diabetes. , 2007, The Journal of clinical investigation.

[10]  N. Agrawal,et al.  A Functional Single Nucleotide Polymorphism -1562C>T in the Matrix Metalloproteinase-9 Promoter Is Associated With Type 2 Diabetes and Diabetic Foot Ulcers , 2013, The international journal of lower extremity wounds.

[11]  S. R. Kulkarni,et al.  Common variants in the TCF7L2 gene are strongly associated with type 2 diabetes mellitus in the Indian population , 2006, Diabetologia.

[12]  J. Fallon,et al.  Molecular pathogenesis of chronic wounds: the role of beta-catenin and c-myc in the inhibition of epithelialization and wound healing. , 2005, The American journal of pathology.

[13]  P. O'Connell,et al.  Linkage of type 2 diabetes mellitus and of age at onset to a genetic location on chromosome 10q in Mexican Americans. , 1999, American journal of human genetics.

[14]  G. Novelli,et al.  TCF7L2 gene polymorphisms and type 2 diabetes: association with diabetic retinopathy and cardiovascular autonomic neuropathy , 2013, Acta Diabetologica.

[15]  B. Alman,et al.  Beta‐catenin regulates wound size and mediates the effect of TGF‐beta in cutaneous healing , 2006, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[16]  W D Thompson,et al.  Expression of Wnt genes in early wound healing , 1998, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[17]  Philippe Froguel,et al.  TCF7L2 is reproducibly associated with type 2 diabetes in various ethnic groups: a global meta-analysis , 2007, Journal of Molecular Medicine.

[18]  B. Alman,et al.  Beta-catenin is a mediator of the response of fibroblasts to irradiation. , 2009, The American journal of pathology.

[19]  T. Jin,et al.  The Wnt signaling pathway effector TCF7L2 and type 2 diabetes mellitus. , 2008, Molecular endocrinology.

[20]  R. G. Paul,et al.  Biomechanical and biochemical study of a standardized wound healing model. , 1997, The international journal of biochemistry & cell biology.

[21]  D. Moczulski,et al.  TCF7L2 gene is associated with type 2 diabetes in Polish population , 2007 .

[22]  M. Małecki Genetics of type 2 diabetes mellitus. , 2005, Diabetes research and clinical practice.

[23]  H. Stefánsson,et al.  Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes , 2006, Nature Genetics.

[24]  A. Książek,et al.  Transcription factor 7-like 2 (TCF7L2) gene polymorphism and complication/comorbidity profile in type 2 diabetes patients. , 2011, Diabetes research and clinical practice.

[25]  William R. Ledoux,et al.  Epidemiology of Diabetic Foot Ulcers and Amputations: Evidence for Prevention , 2003 .

[26]  A. Boulton The diabetic foot: from art to science. The 18th Camillo Golgi lecture , 2004, Diabetologia.

[27]  O. Hansson,et al.  Molecular Function of TCF7L2: Consequences of TCF7L2 Splicing for Molecular Function and Risk for Type 2 Diabetes , 2010, Current diabetes reports.

[28]  A. Boulton,et al.  The global burden of diabetic foot disease , 2005, The Lancet.

[29]  M. A. Kelly,et al.  Common variants of the TCF7L2 gene are associated with increased risk of type 2 diabetes mellitus in a UK-resident South Asian population , 2008, BMC Medical Genetics.

[30]  N. Agrawal,et al.  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 , 2013, BioMed research international.

[31]  S. Rensen,et al.  Wnt/frizzled signalling modulates the migration and differentiation of immortalized cardiac fibroblasts. , 2010, Cardiovascular research.

[32]  P. Howe,et al.  Wnt Signaling: Physiology and Pathology , 2004, Growth factors.

[33]  C. Wang,et al.  Effect of Wnt signaling pathway on wound healing. , 2009, Biochemical and biophysical research communications.

[34]  B. Thiers Wnt-dependent de novo hair follicle regeneration in adult mouse skin after wounding , 2008 .

[35]  T. Winder,et al.  Single Nucleotide Polymorphisms of TCF7L2 Are Linked to Diabetic Coronary Atherosclerosis , 2011, PloS one.