PMID- 21380725
OWN - NLM
STAT- MEDLINE
DCOM- 20111018
LR  - 20220409
IS  - 1573-4919 (Electronic)
IS  - 0300-8177 (Linking)
VI  - 353
IP  - 1-2
DP  - 2011 Jul
TI  - Interaction of eNOS polymorphism with MTHFR variants increase the risk of 
      diabetic nephropathy and its progression in type 2 diabetes mellitus patients.
PG  - 23-34
LID - 10.1007/s11010-011-0770-0 [doi]
AB  - The present study has investigated the role of endothelial nitric oxide (eNOS) 
      G894T polymorphism and its interaction with methylenetetrahydrofolate reductase 
      (MTHFR) C677T and A1298C variants on the predisposition to diabetic nephropathy 
      and its progression. Using polymerase chain reaction-restriction fragment length 
      polymorphism (PCR-RFLP) method the eNOS G894T and MTHFR polymorphisms were 
      detected in 72 microalbuminuric, 68 macroalbuminuric, and 72 normoalbuinuric type 
      2 diabetes mellitus (T2DM) patients from Western Iran. The presence of GT and GT 
      + TT genotypes of eNOS were associated with insignificantly 1.86- and 1.68-fold 
      increased risk of macroalbuminuria, respectively and 1.21- and 1.13-fold 
      increased risk of microalbuminuria, respectively. However, the concomitant 
      presence of eNOST and MTHFR 1298C alleles were significantly increased the risk 
      of macroalbuminuria (6.6-fold, P < 0.001) and progression from micro- to 
      macro-albuminuria (3.85 times, P = 0.011). Also, the presence of both alleles of 
      eNOST and MTHFR 677T were significantly associated with increased risk of 
      macroalbuminuria (4.8-fold, P = 0.005). The presence of GT + TT genotypes of eNOS 
      was significantly associated with increased risk of coronary artery disease in 
      micro- and macro-albuminuric patients compared to normoalbuminuric patients. The 
      concomitant presence of three mutant alleles significantly increased the risk of 
      macroalbuminuria and progression from micro- to macro-albuminuria 38.5- and 
      10.5-fold, respectively. Our study indicated that eNOS T allele interacts with 
      MTHFR variants, especially MTHFR A1298C to increase the risk of macroalbuminuria 
      and progression from micro-to macro-albuminuria. Also, Interaction between three 
      alleles of eNOST, MTHFR 677T, and 1298C highly increased the risk of 
      macroalbuminuria and progression of diabetic nephropathy in T2DM patients.
FAU - Jafari, Yazdan
AU  - Jafari Y
AD  - Medical Biology Research Center, Kermanshah University of Medical Sciences, 
      Kermanshah, Iran.
FAU - Rahimi, Zohreh
AU  - Rahimi Z
FAU - Vaisi-Raygani, Asad
AU  - Vaisi-Raygani A
FAU - Rezaei, Mansour
AU  - Rezaei M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110306
PL  - Netherlands
TA  - Mol Cell Biochem
JT  - Molecular and cellular biochemistry
JID - 0364456
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 1.5.1.20 (Methylenetetrahydrofolate Reductase (NADPH2))
SB  - IM
MH  - Aged
MH  - Albuminuria/complications/genetics/pathology
MH  - Diabetes Mellitus, Type 2/*complications
MH  - Diabetic Nephropathies/complications/*genetics/pathology
MH  - Disease Progression
MH  - Epistasis, Genetic
MH  - Female
MH  - Gene Frequency
MH  - Genetic Predisposition to Disease
MH  - Genotype
MH  - Humans
MH  - Male
MH  - Methylenetetrahydrofolate Reductase (NADPH2)/*genetics
MH  - Middle Aged
MH  - Nitric Oxide Synthase Type III/*genetics
MH  - Odds Ratio
MH  - Polymerase Chain Reaction
MH  - Polymorphism, Restriction Fragment Length
MH  - *Polymorphism, Single Nucleotide
MH  - Risk Assessment
MH  - Risk Factors
EDAT- 2011/03/08 06:00
MHDA- 2011/10/19 06:00
CRDT- 2011/03/08 06:00
PHST- 2010/09/30 00:00 [received]
PHST- 2011/02/24 00:00 [accepted]
PHST- 2011/03/08 06:00 [entrez]
PHST- 2011/03/08 06:00 [pubmed]
PHST- 2011/10/19 06:00 [medline]
AID - 10.1007/s11010-011-0770-0 [doi]
PST - ppublish
SO  - Mol Cell Biochem. 2011 Jul;353(1-2):23-34. doi: 10.1007/s11010-011-0770-0. Epub 
      2011 Mar 6.