Endothelial nitric oxide synthase (eNOS) 4b/a gene polymorphism and the risk of diabetic nephropathy in type 2 diabetes
AbstractDiabetic Nephropathy (DN) poses a major health problem. There is strong evidence for a potential role of the eNOS gene. The aim of this case control study was to investigate the possible role of genetic variants of the endothelial Nitric Oxide Synthase (eNOS) gene (VNTR) in the pathogenesis of nephropathy in patients with diabetes mellitus. The study included 196 subjects (145 T2DM and 51 normal controls) T2DM were classified into 2 groups: 97 diagnosed with DN, and 48 diabetics without nephropathy and hypertension as +ve control. Randomly selected was conducted to assess the association of SNP eNOS intron 4a/b VNTR polymorphism gene with diabetic nephropathy in Iraqi population. Blood samples from subjects and controls were analyzed to investigate the eNOS genotypes No significant differences were found in the frequency of eNOS genotypes between diabetic patients (either in group 1 or group 2) and controls (p >0.05). Also, no significant differences were found in the frequency of eNOS genotypes between group 1 and group 2 (p >0.05).
Rambhade S., Chakraborty A. K., Patil U. K., et al. Diabetes Mellitus- Its complications, factors influencing complications and prevention- An Overview. J. Chem. Pharm. Res., 2010, 2(6):7-25.
Phillip MH. Prevention of Progression in Diabetic Nephropathy Diabetes Spectrum. 2006; 19(1): 18-24.
Forbes J M, Fukami K, Cooper M E. Diabetic Nephropathy: Where Hemodynamics Meets Metabolism. Exp Clin Endocrinol Diabetes 2007; 00:1 – 16.
Edmund JL Xiulong, X. Abnormal glomerular permeability characteristics in diabetic nephropathy: Implication for the therapeutic use of the low- molecular weight heparin Diabetes Care.2008; 31(2): S202–S207.
Dellamea B S, Ferreira Pinto L C, Leitão C B, et al. Endothelial nitric oxide synthase gene polymorphisms and risk of diabetic nephropathy: a systematic review and meta-analysis. BMC Medical Genetics. 2014, 15:9.
Bredt DS, Snyder SH: Nitric oxide: a physiologic messenger molecule. Annu Rev Biochem 1994, 63:175–195.
Tsutsui M, et al: Nitric oxide synthases and cardiovascular diseases: insights from genetically modified mice. Circ J 2009, 73(6):986–993.
Napoli C, Ignarro LJ: Nitric oxide and pathogenic mechanisms involved in the development of vascular diseases. Arch Pharm Res 2009, 32(8):1103–1108.
Huang PL: eNOS, metabolic syndrome and cardiovascular disease. Trends Endocrinol Metab .2009; 20(6):295–302.
MA Z, Chen R, Ren H, et al. Endothelial nitric oxide synthase (eNOS) 4b/a polymorphism and the risk of diabetic nephropathy in type 2 diabetes mellitus: A meta-analysis. Meta Gene. (2014);2: 50–62.
Yoon Y, Song J, Hong SH, Kim JQ. Plasma nitric oxide concentrations and nitric oxide synthase gene polymorphisms in coronary artery disease. Clin Chem .2000; 46: 1626-30.
Wang XL, Mahaney MC, Sim AS, et al. Genetic contribution of the endothelial constitutive nitric oxide synthase gene to plasma nitric oxide levels. Arterioscler Thromb Vasc Biol .1997; 17: 3147-53.
Bolli P, Sticchi E, Abbate R, et al. A novel allele of eNOS gene in the Italian population: the actual essence of intron 4 polymorphism. Nitric Oxide. 2007; 16: 392-4.
Volgelstein, B., and Gillespie, D. (1979) Pro. Natl. Acad. Sci. USA 76.
Thompson, Margaret W., Roderick R. McInnes, and Huntington F. Willard. 1991. Thompson & Thompson genetics in medicine. Fifth ed. Philadelphia: W. B. Saunders.
Shah V N, Cheema B S, Kohli H S, et al. Endothelial Nitric Oxide Synthase Gene polymorphism and the risk of diabetic Neuropathy in Asian Indian Patients with Type 2 Diabetes. 2013. J Diabetes Metab. 4.2.
Neugebauer S, Baba T, and Watanabe T. Association of the Nitric Oxide Synthase Gene Polymorphism with an Increased Risk for Progression to Diabetic Nephropathy in Type 2 Diabetes. Diabetes. 2000: 49:500–5030.
Bernhard Degen, Susanne Schmidt, Eberhard Ritz. A polymorphism in the gene for the endothelial nitric oxide synthase and diabetic nephropathy. Nephro Dia Transplant .2001.16:185-198.
Ksiazek P, et al: Endothelial nitric oxide synthase gene intron 4 polymorphism in type 2 diabetes mellitus. Mol Diagn 2003, 7(2):119–123.
Ezzidi I, Mtiraoui N, Mohamed MBH, et al. Association of endothelial nitric oxide synthase Glu298Asp, 4b/a, and -786 T > C gene variants with diabetic nephropathy. J Diabetes Complications. 2008; 22(5):331–338.
Elias Zintzaras Impact of Hardy-Weinberg equilibrium deviation on allelebased risk effect of genetic association studies and meta-analyses, European Journal of Epidemiology 25, 8 (2010) 553-560.
Buraczynska M, Ksiazek P, Zaluska W, et al. Endothelial nitric oxide synthase gene intron 4 polymorphism in patients with end-stage renal disease. Nephrol Dial Transplant (2004) 19: 2302–2306.
Ahluwalia, T. S., Ahuja, M., Rai, T. S., Kohli, H. S., Sud, K., Bhansali, A. and Khullar, M. Endothelial nitric oxide synthase gene haplotypesand diabetic nephropathy among Asian Indians. Mol. Cell Biochem.2008; 314, 9–17.
ShoukryA, Shalaby S M, Abdelazim S, et al. Endothelial Nitric Oxide Synthase Gene Polymorphisms and the Risk of Diabetic Nephropathy in Type 2 Diabetes Mellitus. Genetic Testing and Molecular Biomarkers.2012;16(6): 574–579.
Lin S, Qu H, Qiu M. Allele A in intron 4 of ecNOS gene will not increase the risk of DN in type 2 diabetes of Chinese population. Nephron.2002; 91:768.
Rahimi, Z., Rahimi, Z., Shahvaisi-Zadeh, F., Sadeghei, S., Vessal, M., Yavari, N., 2013. eNOS 4a/b polymorphism and its interaction with eNOS G894T variants in type 2 diabetes mellitus: modifying the risk of diabetic nephropathy. Dis. Markers.2013; 34, 437–443.
Taniwaki H, Ishimura E, Matsumoto N, et al. Relations Between ACE Gene and ecNOS Gene Polymorphisms and Resistive Index in Type 2 Diabetic Patients with Nephropathy. Diabetes Care .2001; 24:1653–1660.