Diabetes prominent indication of it is hyperglycemia [1].

Diabetes mellitus is a metabolic disorderthat the prominent indication of it is hyperglycemia 1. The number of patients withdiabetes mellitus in 2010 was 285 million, which is projected to reach to 439million in 20302, 3.Diabeticnephropathy(DN) is one of the rampant microvascular complications of diabetesmellitus, which affects 25-40% of people with type 2 diabetes1, 4. Steady Increase in urine albumin, hypertension, anddecrease in Glomerular filtration rate(GFR) are the major appearances ofdiabetic nephropathy which eventually leads to end-stage renal disease (ESRD)4-6. Diabetic nephropathy is a complicateddisease because both the genes and the environment are involved in thesusceptibility to the disease 7, 8.Onthe other, the high prevalence of Diabetic nephropathy in some ethnic groupssuch as Pima Indians and African Americans have been reported by familial clusteringand ethnic studies 9, 10. Methylene tetrahydrofolatereductase (MTHFR) gene which converts 5, 10-methylenetetrahydrofolate to5-methyltetrahydrofolate is one of the candidate genes that associates withdiabetic nephropathy 9, 11. The C677T (rs1801133)polymorphism is located in exon number 4 which converts alanine 222 to valine12.

C677T polymorphismreduces the thermostability of MTHFR enzyme in normal body temperature(37° C). TheTT genotype approximately reduced MTHFR activity by 50 to 60% at 37 ° C andmore than 65% at 46 ° C13. rs1801133 facilitatesthe loss of flavin adenine nucleotide (FAD) cofactor which results inthermosensitive protein14.

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C677T polymorphism has beenreported in different populations that leads to hyperhomocysteinemia during folate deficiency15, 16. Homocysteine,through the production of Reactive oxygen species, reduces the life ofinsulin-producing cells, which ultimately leads to reduced glucokinasephosphorylation activity, decreased sensitivity to insulin secretion and celldeath17. Increase in age, male gender,coffee consumption, high blood pressure, high creatinine, vitamin B6, B12,folate deficiency and C677T polymorphism are all associated with increase inplasma homocysteine 18. In addition, diabeticnephropathy has been shown to be the most important factor in increasing thetotal homocysteine concentration in a patient with type 2 diabetes, as kidney’sability to clear homocysteine is reduced in nephropathic patients. In this study, we investigated therole of C677T polymorphism with diabetic nephropathy and plasma homocysteine inIranian population.