Introduction in Glomerular filtration rate(GFR) are the major

Introduction

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 nephropathyFif.1 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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Introduction

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 nephropathyFif.1 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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For You For Only $13.90/page!


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