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Gene. 2013 Apr 25;519(1):187-93. doi: 10.1016/j.gene.2013.01.004. Epub 2013 Jan 29.

The polymorphism for endothelial nitric oxide synthase gene, the level of nitric oxide and the risk for pre-eclampsia: a meta-analysis.

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Department of Epidemiology and Health Statistics, School of Public Health, Shandong University, 44 Wenhua Xi Road, Ji'nan, Shandong 250012, PR China.


Endothelial NO, which is synthesized by endothelial nitric oxide synthase (eNOS), has been reported to be related with the occurrence of pre-eclampsia (PE). However, the polymorphisms of eNOS (-786 T>C, 4b/a and G894T), the level of nitric oxide and the risk of PE remain unclear. Thus we performed this meta-analysis to determine the associations between them in order to predict the risk for PE and interference with PE development in the early period of antenatal care. All studies investigating the associations between PE risk and polymorphisms of eNOS, or PE risk and serum concentration of NO were reviewed. Finally, 29 studies were included, involving 11 for -786 T>C, 11 for 4b/a, and 22 for G894T polymorphisms and PE risk. In the overall analysis, -786 T>C polymorphism was found to be related with increased PE risk in the dominant model (OR=1.17, 95% CI=1.02-1.35). a allele for 4b/a suffers the high risk of PE (OR=1.46, 95% CI=1.01-2.10). In the subgroup analysis, significantly increased risk was detected among Europeans for -786 T>C polymorphism (OR=1.40, 95%CI=1.14-1.73).However, no significant association was detected for G894T polymorphism in the overall and subgroup analysis. The comprehensive evaluation of 9 available studies indicated that serum NO level was significantly decreased in case group (SMD=-0.96 umol/mL, 95%CI=-1.80, -0.12 umol/mL).Hence, we concluded that eNOS gene -786 T>C and 4b/a except for G894T polymorphisms were contributed significantly to PE risk, especially for Europeans, and a low NO concentration in serum increased the risk for PE.

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