Women with a particular variation in a gene that controls the way that blood vessels function have a 60% greater risk of recurrent miscarriage, Professor Clemens Tempfer and colleagues from the University of Vienna School of Medicine report in Europe's leading reproductive medicine journal, Human Reproduction.*
Nearly a fifth of all pregnancies end in miscarriages, but up to two per cent of women suffer recurrent miscarriages i.e. three or more consecutive pregnancy losses before 20 weeks. The research team has found evidence that a variation in a gene - NOS - which is known to be involved in synthesising nitric oxide, could be at least partly to blame.
They compared a group of 105 women who had all suffered recurrent spontaneous miscarriages with a carefully matched control group of 91 postmenopausal women who had never had a miscarriage and who had given birth at least twice.
"Nitric oxide has been implicated in blood vessel disease and damage and nitric oxide synthase (NOS) is known to mediate vascular relaxation," said Professor Tempfer: "We found a significant difference in the genotype frequencies for one variation of the NOS3 gene between the study and control groups."
"This is evidence of a relationship between unexplained recurrent miscarriage and a gene, the product of which is already known to influence the way vascular smooth muscles behave. Given also the role that nitric oxide deficiency plays in high blood pressure, haemorrhage, vascular spasms and infarction, it's reasonable to speculate that carriers of an NOS3 polymorphism are at increased risk for impaired placental function. Displaying this polymorphism is not necessary or sufficient on its own for the development of unexplained recurrent miscarriages, but our data indicate that it does confer a small (1.6-fold) but significantly increased risk.
Professor Tempfer concluded that the findings also added further evidence that endothelium-derived nitric oxide plays a mediating role in early pregnancy. "Identifying a link between unexplained recurrent miscarriages and a specific variant of a gene involved in the regulation of placental function and the stability of the vascular 'environment' is going to give us further insight into this syndrome and more information about susceptible women," he said.
* Endothelial nitric oxide synthase gene polymorphism in women with idiopathic recurrent miscarriage. Human Reproduction Vol 16. No 8. pp 1644-1647.
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