Human Genetics

, Volume 127, Issue 4, pp 373–381 | Cite as

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

Review Article

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.

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

Supplementary material

439_2009_783_MOESM1_ESM.doc (82 kb)
Supplementary figure (DOC 81.5 kb)
439_2009_783_MOESM2_ESM.doc (92 kb)
Supplementary table (DOC 91.5 kb)

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Zhen Zeng
    • 1
    • 2
    • 3
  • Lina Li
    • 4
  • Zhao Zhang
    • 1
    • 2
    • 3
  • Yang Li
    • 1
    • 2
    • 3
  • Zhiyun Wei
    • 1
    • 2
    • 3
  • Ke Huang
    • 1
    • 2
    • 3
  • Lin He
    • 1
    • 2
    • 3
    • 5
  • Yongyong Shi
    • 1
    • 2
    • 3
  1. 1.Bio-X CenterShanghai Jiao Tong UniversityShanghaiPeople’s Republic of China
  2. 2.Affiliated Changning Mental Health Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education)Shanghai Jiao Tong UniversityShanghaiPeople’s Republic of China
  3. 3.Institute for Nutritional Sciences, Shanghai Institutes of Biological SciencesChinese Academy of SciencesShanghaiPeople’s Republic of China
  4. 4.Department of Biological Science and BiotechnologyTsinghua UniversityBeijingPeople’s Republic of China
  5. 5.Institutes of Biomedical SciencesFudan UniversityShanghaiPeople’s Republic of China

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