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Interaction of eNOS polymorphism with MTHFR variants increase the risk of diabetic nephropathy and its progression in type 2 diabetes mellitus patients

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Abstract

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.

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Acknowledgment

This work was financially supported by a grant from Vice Chancellor for Research of Kermanshah University of Medical Sciences, Kermanshah, Iran.

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Authors and Affiliations

  1. Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran

    Yazdan Jafari & Zohreh Rahimi

  2. Department of Pharmacology, School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran

    Yazdan Jafari

  3. Department of Biochemistry, Medical School, Kermanshah University of Medical Sciences, Daneshgah Avenue, P.O. Box 67148-69914, Kermanshah, Iran

    Zohreh Rahimi & Asad Vaisi-Raygani

  4. Department of Biostatistics, Medical School, Kermanshah University of Medical Sciences, Kermanshah, Iran

    Mansour Rezaei

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  1. Yazdan Jafari
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  2. Zohreh Rahimi
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  4. Mansour Rezaei
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Correspondence to Zohreh Rahimi.

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Jafari, Y., Rahimi, Z., Vaisi-Raygani, A. et al. Interaction of eNOS polymorphism with MTHFR variants increase the risk of diabetic nephropathy and its progression in type 2 diabetes mellitus patients. Mol Cell Biochem 353, 23–34 (2011). https://doi.org/10.1007/s11010-011-0770-0

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