A Meta-analysis of Three Polymorphisms in the Endothelial Nitric Oxide Synthase Gene (NOS3) and Their Effect on the Risk of Diabetic Nephropathy

Overview

Journal Hum Genet

Specialty Genetics

Date 2010 Jan 6

PMID 20049477

Citations 16

Authors

Zhen Zeng

Lina Li

Zhao Zhang

Yang Li

Zhiyun Wei

Ke Huang

Lin He

Yongyong Shi

Affiliations

Soon will be listed here.

Abstract

A number of association studies have investigated the role of the nitric oxide synthase 3 (NOS3) gene in the development of diabetic nephropathy (DN). However, results have been inconclusive, largely because the studies have focused on a variety of different polymorphisms and generate inconsistent results. We performed a meta-analysis of 28 association studies focusing on three polymorphisms in the NOS3 gene (G894T (Glu289Asp), 4b/a, and T-786C) and the risk of DN published before July 2009, covering a total of 10,364 subjects. Although significant heterogeneity was initially found in the analysis of G894T, it did not remain when analysis was done by ethnic subgroups. 894T was negatively associated with DN in Caucasian populations of European origin (OR = 0.896, 0.817-0.983, 95% CI), but was positively associated with DN in East Asian (OR = 2.02, 1.20-3.42, 95% CI) and other populations. Association of the 4b/a variant was observed when studies involving microalbuminuria were excluded (OR = 1.19, 1.02-1.39, 95% CI). The T-786C variant showed an overall weak association (OR = 1.16, 1.01-1.34, 95% CI) with little heterogeneity. In summary, our meta-analysis of the effect of NOS3 gene polymorphisms on the risk of DN supports the involvement of the NOS3 gene in the pathogenesis of DN.

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References

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

Begg C, Mazumdar M . Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994; 50(4):1088-101. View

Miyamoto Y, Saito Y, Nakayama M, Shimasaki Y, Yoshimura T, Yoshimura M . Replication protein A1 reduces transcription of the endothelial nitric oxide synthase gene containing a -786T-->C mutation associated with coronary spastic angina. Hum Mol Genet. 2000; 9(18):2629-37. DOI: 10.1093/hmg/9.18.2629. View

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

Nath S, He X, Saroja Voruganti V, Blangero J, MacCluer J, Comuzzie A . The 27-bp repeat polymorphism in intron 4 (27 bp-VNTR) of endothelial nitric oxide synthase (eNOS) gene is associated with albumin to creatinine ratio in Mexican Americans. Mol Cell Biochem. 2009; 331(1-2):201-5. PMC: 3428139. DOI: 10.1007/s11010-009-0159-5. View

WOOLF B . On estimating the relation between blood group and disease. Ann Hum Genet. 1955; 19(4):251-3. DOI: 10.1111/j.1469-1809.1955.tb01348.x. View

Wang J, Dudley D, Wang X . Haplotype-specific effects on endothelial NO synthase promoter efficiency: modifiable by cigarette smoking. Arterioscler Thromb Vasc Biol. 2002; 22(5):e1-4. PMC: 1350055. DOI: 10.1161/01.atv.0000016248.51577.1f. View

Degen B, Schmidt S, Ritz E . A polymorphism in the gene for the endothelial nitric oxide synthase and diabetic nephropathy. Nephrol Dial Transplant. 2001; 16(1):185. DOI: 10.1093/ndt/16.1.185. View

DerSimonian R, Laird N . Meta-analysis in clinical trials. Control Clin Trials. 1986; 7(3):177-88. DOI: 10.1016/0197-2456(86)90046-2. View

10.

Mohan S, Reddick R, Musi N, Horn D, Yan B, Prihoda T . Diabetic eNOS knockout mice develop distinct macro- and microvascular complications. Lab Invest. 2008; 88(5):515-28. DOI: 10.1038/labinvest.2008.23. View

11.

Prabhakar S . Role of nitric oxide in diabetic nephropathy. Semin Nephrol. 2004; 24(4):333-44. DOI: 10.1016/j.semnephrol.2004.04.005. View

12.

Mamoulakis D, Bitsori M, Galanakis E, Vazgiourakis V, Panierakis C, Goulielmos G . Intron 4 polymorphism of the endothelial nitric oxide synthase eNOS gene and early microangiopathy in type 1 diabetes. Int J Immunogenet. 2009; 36(3):153-7. DOI: 10.1111/j.1744-313X.2009.00839.x. View

13.

Nakagawa T . Uncoupling of the VEGF-endothelial nitric oxide axis in diabetic nephropathy: an explanation for the paradoxical effects of VEGF in renal disease. Am J Physiol Renal Physiol. 2007; 292(6):F1665-72. DOI: 10.1152/ajprenal.00495.2006. View

14.

Jawa A, Kcomt J, Fonseca V . Diabetic nephropathy and retinopathy. Med Clin North Am. 2004; 88(4):1001-36, xi. DOI: 10.1016/j.mcna.2004.04.012. View

15.

Taverna M, Sola A, Guyot-Argenton C, Pacher N, Bruzzo F, Chevalier A . eNOS4 polymorphism of the endothelial nitric oxide synthase predicts risk for severe diabetic retinopathy. Diabet Med. 2002; 19(3):240-5. DOI: 10.1046/j.1464-5491.2002.00681.x. View

16.

Shi Y, Zhao X, Yu L, Tao R, Tang J, La Y . Genetic structure adds power to detect schizophrenia susceptibility at SLIT3 in the Chinese Han population. Genome Res. 2004; 14(7):1345-9. PMC: 442150. DOI: 10.1101/gr.1758204. View

17.

Seaquist E, Goetz F, Rich S, Barbosa J . Familial clustering of diabetic kidney disease. Evidence for genetic susceptibility to diabetic nephropathy. N Engl J Med. 1989; 320(18):1161-5. DOI: 10.1056/NEJM198905043201801. View

18.

Santilli F, Cipollone F, Mezzetti A, Chiarelli F . The role of nitric oxide in the development of diabetic angiopathy. Horm Metab Res. 2004; 36(5):319-35. DOI: 10.1055/s-2004-814489. View

19.

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

20.

Tiwari A, Prasad P, B K T, Prasanna Kumar K, Ammini A, Gupta A . Oxidative stress pathway genes and chronic renal insufficiency in Asian Indians with Type 2 diabetes. J Diabetes Complications. 2008; 23(2):102-11. DOI: 10.1016/j.jdiacomp.2007.10.003. View