Association between Nitric Oxide Production in Preeclampsia and Variations in the Endothelial Nitric Oxide Synthase Gene

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Background: Preeclampsia (PE) is a multifactorial hypertensive pregnancy illness.Many factors are involved in regulating endothelial function; however, the development of PE appears to be primarily influenced by the endothelial nitric oxide synthase (eNOS) gene.This study examined the association of the eNOS 4b/4a, eNOS 894G>T, and eNOS -786T>C variants with the susceptibility of PE in Egyptian pregnant women, as well as their relation with the lab measurements and clinical manifestations of the disease.Patients and methods: DNA was isolated from blood samples of 136 Egyptian pregnant women with PE and also from 100 age-matched women with uncomplicated pregnancy.The presence of eNOS 4b/4a, eNOS 894G>T, and eNOS -786T>C variants was examined by polymerase chain reaction (PCR)-based assay.In addition, serum nitric oxide (NO) and antioxidants were assessed by the enzyme-linked immunosorbent assay technique.Results: The main findings were reduced concentrations of NO and the antioxidants [superoxide dismutase (SOD), glutathione reductase, and glutathione peroxidase (GPx)] in the PE group than in the uncomplicated pregnancy group (p < 0.001 for all).When eNOS (-786T>C) and (4b/4a) variants were genotyped, no apparent variance between the two groups was observed.The combination of diverse genetic association models showed that PE was linked to the eNOS 894G>T polymorphism; the dominant genotype model (GT+ TT vs GG, OR=1.88, p = 0.03) and the allelic model (T-allele vs G-allele, OR=1.92, p = 0.007). Conclusion:The 894G>T single nucleotide polymorphism (SNP) of the eNOS gene was associated with a high risk for PE among Egyptian pregnant women.This variant was associated with reduced NO levels and other antioxidants, SOD, and GPx among the PE cases.

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