Association of the Endothelial Nitric Oxide Synthase Gene G894T Polymorphism with the Risk of Diabetic Nephropathy in Qassim Region, Saudi Arabia-A Pilot Study

Overview

Journal Meta Gene

Publisher Elsevier

Specialty Genetics

Date 2015 Jan 22

PMID 25606424

Citations 6

Authors

Amal Mohammed Husein Mackawy

Amjad Ali Khan

Mohammed El-Sayed Badawy

Affiliations

Soon will be listed here.

Abstract

Background: Diabetic nephropathy (DN) is a chronic microangiopathic complication of type 2 diabetes mellitus (DM).Vascular endothelial dysfunction resulting from impaired nitric oxide synthase (NOS) activity in the vascular endothelial cells has been suggested as playing an important role in the pathogenesis of diabetic nephropathy (DN). Endothelial nitric oxide synthase (E-NOS) gene G894T polymorphism has been reported to be associated with endothelial dysfunction leading to DN. Our objective was to evaluate the association of G894T polymorphism of eNOS gene with the risk of DN among type 2 diabetic Saudi patients.

Methods: One hundred and twenty subjects were included in this study. They were divided into three groups. Group I, 40 controls. Group II, 40 type 2 diabetic patients without nephropathy. Group III, 40 type2 diabetic patients with nephropathy. Endothelial nitric oxide synthase (eNOS) G894Tpolymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Plasma nitric oxide (NO) levels were estimated.

Results: E-NOS genotype frequency showed non-significant differences among the all studied groups (p > 0.05). Both diabetic groups had significantly higher plasma nitrate levels than in controls with a significant increase in group III than in group II patients (all p < 0.0001). E NOS 894TT genotype was associated with higher plasma nitrate levels in all groups.

Conclusion: E-NOS gene SNP is not considered as genetic risk factor for DN among type 2 diabetic Saudi patients. The higher plasma levels of nitrates as a marker of oxidative stress in diabetic patients with nephropathy suggest the possible role of oxidative stress but not e-NOS gene SNP in pathogenesis of the DN.

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References

Moon J, Yoon S, Kim E, Shin C, Jo S, Jo I . Lack of evidence for contribution of Glu298Asp (G894T) polymorphism of endothelial nitric oxide synthase gene to plasma nitric oxide levels. Thromb Res. 2002; 107(3-4):129-34. DOI: 10.1016/s0049-3848(02)00208-6. View

Veelken R, Hilgers K, Hartner A, Haas A, Bohmer K, Sterzel R . Nitric oxide synthase isoforms and glomerular hyperfiltration in early diabetic nephropathy. J Am Soc Nephrol. 2000; 11(1):71-79. DOI: 10.1681/ASN.V11171. View

Gross J, de Azevedo M, Silveiro S, Canani L, Caramori M, Zelmanovitz T . Diabetic nephropathy: diagnosis, prevention, and treatment. Diabetes Care. 2004; 28(1):164-76. DOI: 10.2337/diacare.28.1.164. View

Rossi G, Taddei S, Virdis A, Cavallin M, Ghiadoni L, Favilla S . The T-786C and Glu298Asp polymorphisms of the endothelial nitric oxide gene affect the forearm blood flow responses of Caucasian hypertensive patients. J Am Coll Cardiol. 2003; 41(6):938-45. DOI: 10.1016/s0735-1097(02)03011-5. View

Drexler H, Hornig B . Endothelial dysfunction in human disease. J Mol Cell Cardiol. 1999; 31(1):51-60. DOI: 10.1006/jmcc.1998.0843. View

Ritt M, Ott C, Delles C, Schneider M, Schmieder R . Impact of the endothelial nitric oxide synthase gene G894T polymorphism on renal endothelial function in patients with type 2 diabetes. Pharmacogenet Genomics. 2008; 18(8):699-707. DOI: 10.1097/FPC.0b013e32830500b1. View

McLennan S, Fisher E, Martell S, Death A, Williams P, Lyons J . Effects of glucose on matrix metalloproteinase and plasmin activities in mesangial cells: possible role in diabetic nephropathy. Kidney Int Suppl. 2000; 77:S81-7. DOI: 10.1046/j.1523-1755.2000.07713.x. View

Bhanoori M . Endothelial nitric oxide synthase (eNOS) variants in cardiovascular disease: pharmacogenomic implications. Indian J Med Res. 2011; 133:464-6. PMC: 3121274. View

Villa L, Salas E, Darley-Usmar V, Radomski M, Moncada S . Peroxynitrite induces both vasodilatation and impaired vascular relaxation in the isolated perfused rat heart. Proc Natl Acad Sci U S A. 1994; 91(26):12383-7. PMC: 45442. DOI: 10.1073/pnas.91.26.12383. View

10.

Manolio T, Brooks L, Collins F . A HapMap harvest of insights into the genetics of common disease. J Clin Invest. 2008; 118(5):1590-605. PMC: 2336881. DOI: 10.1172/JCI34772. View

11.

Ahluwalia T, Ahuja M, Rai T, Kohli H, Sud K, Bhansali A . Endothelial nitric oxide synthase gene haplotypes and diabetic nephropathy among Asian Indians. Mol Cell Biochem. 2008; 314(1-2):9-17. DOI: 10.1007/s11010-008-9759-8. View

12.

Zintzaras E, Papathanasiou A, Stefanidis I . Endothelial nitric oxide synthase gene polymorphisms and diabetic nephropathy: a HuGE review and meta-analysis. Genet Med. 2009; 11(10):695-706. DOI: 10.1097/GIM.0b013e3181b2046b. View

13.

Noiri E, Satoh H, Taguchi J, Brodsky S, Nakao A, Ogawa Y . Association of eNOS Glu298Asp polymorphism with end-stage renal disease. Hypertension. 2002; 40(4):535-40. DOI: 10.1161/01.hyp.0000033974.57407.82. View

14.

Casas J, Cavalleri G, Bautista L, Smeeth L, Humphries S, Hingorani A . Endothelial nitric oxide synthase gene polymorphisms and cardiovascular disease: a HuGE review. Am J Epidemiol. 2006; 164(10):921-35. DOI: 10.1093/aje/kwj302. View

15.

Zanchi A, Moczulski D, Hanna L, Wantman M, Warram J, Krolewski A . Risk of advanced diabetic nephropathy in type 1 diabetes is associated with endothelial nitric oxide synthase gene polymorphism. Kidney Int. 2000; 57(2):405-13. DOI: 10.1046/j.1523-1755.2000.00860.x. View

16.

Yoon Y, Song J, Hong S, Kim J . Plasma nitric oxide concentrations and nitric oxide synthase gene polymorphisms in coronary artery disease. Clin Chem. 2000; 46(10):1626-30. View

17.

Trinder P . Determination of blood glucose using an oxidase-peroxidase system with a non-carcinogenic chromogen. J Clin Pathol. 1969; 22(2):158-61. PMC: 474026. DOI: 10.1136/jcp.22.2.158. View

18.

Schachinger V, Britten M, Zeiher A . Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease. Circulation. 2000; 101(16):1899-906. DOI: 10.1161/01.cir.101.16.1899. View

19.

Ezzidi I, Mtiraoui N, Ben Hadj Mohamed M, Mahjoub T, Kacem M, Almawi W . Association of endothelial nitric oxide synthase Glu298Asp, 4b/a, and -786T>C gene variants with diabetic nephropathy. J Diabetes Complications. 2008; 22(5):331-8. DOI: 10.1016/j.jdiacomp.2007.11.011. View

20.

Tesauro M, Thompson W, Rogliani P, Qi L, Chaudhary P, Moss J . Intracellular processing of endothelial nitric oxide synthase isoforms associated with differences in severity of cardiopulmonary diseases: cleavage of proteins with aspartate vs. glutamate at position 298. Proc Natl Acad Sci U S A. 2000; 97(6):2832-5. PMC: 16015. DOI: 10.1073/pnas.97.6.2832. View