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Diabetes mellitus is a metabolic disorder
that the prominent indication of it is hyperglycemia 1. The number of patients with diabetes
mellitus in 2010 was 285 million, which is projected to reach to 439 million in
20302, 3.Diabetic
nephropathy(DN) is one of the rampant microvascular complications of diabetes
mellitus, which affects 25-40% of people with type 2 diabetes1, 4. Steady Increase in urine albumin, hypertension, and
decrease in Glomerular filtration rate(GFR) are the major appearances of
diabetic nephropathy which eventually leads to end-stage renal disease (ESRD)4-6. Diabetic nephropathy is a complicated
disease because both the genes and the environment are involved in the
susceptibility to the disease 7, 8.On
the other, the high prevalence of Diabetic nephropathy in some ethnic groups
such as Pima Indians and African Americans have been reported by familial
clustering and ethnic studies 9, 10. Methylene tetrahydrofolate
reductase (MTHFR) gene which converts 5, 10-methylenetetrahydrofolate to
5-methyltetrahydrofolate is one of the candidate genes that associates with
diabetic nephropathy 9, 11. The C677T (rs1801133)
polymorphism is located in exon number 4 which converts alanine 222 to valine12. C677T polymorphism
reduces the thermostability of MTHFR enzyme in normal body temperature(37° C). The
TT genotype approximately reduced MTHFR activity by 50 to 60% at 37 ° C and
more than 65% at 46 ° C13. rs1801133 facilitates
the loss of flavin adenine nucleotide (FAD) cofactor which results in
thermosensitive protein14. C677T polymorphism has been
reported in different populations that leads to 
hyperhomocysteinemia during folate deficiency15, 16. Homocysteine,
through the production of Reactive oxygen species, reduces the life of
insulin-producing cells, which ultimately leads to reduced glucokinase phosphorylation
activity, decreased sensitivity to insulin secretion and cell death17. 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 in
plasma homocysteine 18. In addition, diabetic
nephropathy has been shown to be the most important factor in increasing the
total homocysteine concentration in a patient with type 2 diabetes, as kidney’s
ability to clear homocysteine is reduced in nephropathic patients. In this study, we investigated the
role of C677T polymorphism with diabetic nephropathy and plasma homocysteine in
Iranian population.

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