Human Reproduction, Vol. 16, No. 8, 1644-1647,
August 2001
© 2001 European Society of Human Reproduction and Embryology
Endothelial nitric oxide synthase gene polymorphism in women with idiopathic recurrent miscarriage
1 Department of Gynaecology and Obstetrics and 2 Department of Gynaecologic Endocrinology and Reproductive Medicine, University of Vienna School of Medicine, Waehringer Guertel 18–20, A-1090 Vienna, Austria
BACKGROUND: Lack of endothelium-derived nitric oxide is associated with vasospasm and vascular infarction. We investigated the relationship between idiopathic recurrent miscarriage and a polymorphism of the gene encoding endothelial nitric oxide synthase (NOS3). METHOD: In a prospective case–control study, 105 women with idiopathic recurrent miscarriage and 91 healthy controls were investigated. We used the polymerase chain reaction to identify the different alleles of a 27 base pair tandem repeat polymorphism in intron 4 of the NOS3 gene. RESULTS: The wild type B allele was identified on 329 out of 392 chromosomes (frequency 0.84). The polymorphic A allele was present on 63 chromosomes (frequency 0.16). The genotype frequencies were as follows: 68% (B/B), 31% (A/B) and .5% (A/A). The distribution of genotype frequencies was significantly different between the study and control groups for allele A/B heterozygotes (NOS3A/B) (36.7 versus 23.8%, P = 0.03, OR 1.6, 95% CI 1.1–3.8). Only one individual was homozygous for the A allele (NOS3A/A). She was in the study group. Between women with primary and secondary recurrent miscarriages, no statistically significant difference between the distribution of NOS3A/B genotypes (28 versus 34%) was observed. CONCLUSIONS: These data support a role for the NOS3 gene as a genetic determinant of the risk of idiopathic recurrent miscarriage.
Key words: endothelial nitric oxide synthase/idiopathic recurrent miscarriage/nitric oxide/polymorphism/risk factor
3 To whom correspondence should be addressed. E-mail: fritz.nagele{at}akh-wien.ac.at
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