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Arch Gynecol Obstet. 2008 Oct;278(4):349-52. doi: 10.1007/s00404-008-0577-8. Epub 2008 Feb 26.

Endothelial nitric oxide synthase gene polymorphisms in recurrent spontaneous abortions.

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Division of Genetics, Department of Biology, University of Athens, Athens, Greece.



The risk of miscarriage is enhanced by a variety of genetic and environmental factors. Previous studies indicated an association between endothelial nitric oxide synthase (eNOS) activity, and implantation and maintenance of pregnancy, but it is rather controversial whether polymorphisms of the gene encoding for eNOS are associated with recurrent spontaneous abortions (RSA). The aim of our study was to determine whether the 27 bp intron 4 repeat polymorphism (4VNTR) and a Glu298Asp missense mutation encoded by exon 7 of the eNOS gene are associated with an increased risk for recurrent spontaneous abortions (RSA), in the Greek population.


A total of 126 women who had at least three unexplained spontaneous abortions before 20 weeks of gestation, with the same partner, were included in the study group. The control group consistent of 130 women with at least two live childbirths and without history of abortions. All patients and controls were investigated for the two polymorphisms. To genotype the cohorts we used the PCR-RFLPs method.


The observed frequencies of bb, ba, aa genotypes of the VNTR, in intron 4, polymorphism were 0.75, 0.24, 0.01, respectively, for the patient group and 0.73, 0.24, 0.03, respectively, for the control group. The observed frequencies of GG, GT, TT of the Glu298Asp polymorphism were 0.42, 0.45, 0.13, respectively, for the patient group and 0.47, 0.45, 0.08, respectively, for the control group. Statistical analysis of the results indicates no significant difference between the two groups, for both the two studied polymorphisms.


Our results do not show any influence of the two polymorphisms, VNTR in intron 4 and Glu298Asp of the eNOS gene, on early pregnancy.

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