TCF7L2 Gene Polymorphism and AGEs in Diabetic Nephropathy

Study Overview
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Brief Summary
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To study genotypic distribution of the TCF7L2 gene polymorphism in Diabetic nephropathy. To assess level of AGEs and Insulin in patients with Diabetic nephropathy. To study correlation between polymorphism of the TCF7L2 gene, AGEs, Insulin and clinical characteristics in patients with diabetic nephropathy

Detailed Description
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Diabetic nephropathy is one of microvascular complications of diabetes mellitus. DN is a multifactorial disorder that occurs in one third of patients with long standing DM. DN is one of the most serious complications that being a major contributing factor to end-stage renal disease and death in diabetic patients. The earliest clinical indication of DN is the appearance of microalbuminuria. Detection of diabetic nephropathy as early as possible, is the best chance of delaying progression to ESRD. Thus, screening for microalbuminuria is recommended annually immediately after a diagnosis of diabetes. Transcription factor 7-like 2 is a highly variable transcription factor, which is a key component of the Wnt-signaling pathway and plays a role in the regulation of insulin secretion by pancreatic beta cells and the maintenance of glucose homeostasis. TCF7L2 rs7903146 polymorphism is more associated with T2DM which mediated by decreased insulin secretion associated with defects in insulin processing, reduced effects of glucagon-like peptide-1, increased hepatic glucose production and insulin resistance. The mutant TT genotype and the T allele frequency was associated with diabetic patients who developed nephropathy. Advanced glycation end products are generated by the non-enzymatic reaction of amino groups in DNA and proteins with reducing sugars. AGEs accumulate in glomerular basement membrane. The AGEs-RAGE interaction is a causative factor for DN through activating a series of intracellular signal-cascade pathways which induce the generation of further signalling factors, such as vascular endothelial growth factor, transforming growth factor B, nuclear factor-κβ. Those signalling factors cause mesangial expansion and glomerulosclerosis.

Official Title
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Transcription Factor 7 Like 2 Gene Polymorphism and Advanced Glycation End Products as Risk Factors for Diabetic Nephropathy

Conditions
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Diabetic Nephropathies

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: diabetic nephropathy clinical diagnosis of prediabetes Type 2 diabetic patients Exclusion Criteria: cardiovascular disease diabetic neuropathy diabetic retinopathy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| value of the odds ratio associated with the relationship between a polymorphism TCF7L2 gene and the occurrence of diabetic nephropathy | find a link between genetic polymorphism of TCF7L2 and the risk of developing nephropathy in diabetic patients. Nephropathy is defined Albumin/creatinine ratio > 30 mg/gm creat. | one year | 
| Number of patients with genotype TCF7L2 by PCR | the prevalence of TCF7L2, in the diabetic patient, and compared to the values found in the general population. the TCF7L2 genes will be evaluated by PCR-RFLP | 5 years |