Endothelial nitric oxide synthase gene polymorphism in women with idiopathic recurrent miscarriage.
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).


METHODS
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 (NOS3(A/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 (NOS3(A/A)). She was in the study group. Between women with primary and secondary recurrent miscarriages, no statistically significant difference between the distribution of NOS3(A/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.
Tempfer
C
C
Department of Gynaecology and Obstetrics, University of Vienna School of Medicine, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
Unfried
G
G
Zeillinger
R
R
Hefler
L
L
Nagele
F
F
Huber
J C
JC
D000026:Abortion, Habitual / Q000235:genetics*; D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011446:Prospective Studies; D020080:Tandem Repeat Sequences
C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III