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A meta-analysis of three polymorphisms in the endothelial nitric oxide synthase gene (NOS3) and their effect on the risk of diabetic nephropathy

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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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Abbreviations

DN:

Diabetic nephropathy

DWN:

Diabetes without nephropathy

DM:

Diabetes mellitus

NOS3:

Nitric oxide synthase 3

ESRD:

End-stage renal disease

VNTR:

Variable number tandem repeat

LD:

Linkage disequilibrium

NADT:

No antihypertensive drug treatment

SI:

South Indian

NI:

North Indian

RFLP:

Restriction fragment length polymorphism

TDT:

Transmission disequilibrium test

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Acknowledgments

This work was supported by Grants (2006AA02A407, 2007CB947300, 07DZ22917, 2010CB529600, and 09DJ1400601), the Shanghai Changning Health Bureau Program (2008406002), the Shanghai Municipal Health Bureau Program (2008095), and the Shanghai Leading Academic Discipline Project (B205). Special thanks are due to Dr Tiwari, Prof. T.B.K., Dr Liu, Dr Kaňková, and Prof. Marre for their help in providing the raw data and material from their earlier work.

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Authors and Affiliations

  1. Bio-X Center, Shanghai Jiao Tong University, Central Little White House, 1954 Huashan Road, 200030, Shanghai, People’s Republic of China

    Zhen Zeng, Zhao Zhang, Yang Li, Zhiyun Wei, Ke Huang, Lin He & Yongyong Shi

  2. Affiliated Changning Mental Health Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, 200030, Shanghai, People’s Republic of China

    Zhen Zeng, Zhao Zhang, Yang Li, Zhiyun Wei, Ke Huang, Lin He & Yongyong Shi

  3. Institute for Nutritional Sciences, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, 200031, Shanghai, People’s Republic of China

    Zhen Zeng, Zhao Zhang, Yang Li, Zhiyun Wei, Ke Huang, Lin He & Yongyong Shi

  4. Department of Biological Science and Biotechnology, Tsinghua University, 10084, Beijing, People’s Republic of China

    Lina Li

  5. Institutes of Biomedical Sciences, Fudan University, Ming De Building, 138 Yi Xue Yuan Road, 200032, Shanghai, People’s Republic of China

    Lin He

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  1. Zhen Zeng
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Zeng, Z., Li, L., Zhang, Z. et al. A meta-analysis of three polymorphisms in the endothelial nitric oxide synthase gene (NOS3) and their effect on the risk of diabetic nephropathy. Hum Genet 127, 373–381 (2010). https://doi.org/10.1007/s00439-009-0783-x

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