Endothelial nitric oxide synthase gene influences the risk of pre-eclampsia, the recurrence of negative pregnancy events, and the maternal-fetal flow.
OBJECTIVE
Pre-eclampsia is associated with vascular endothelial dysfunction, adverse pregnancy outcome and cardiovascular disease in later life. An inadequate nitric oxide availability related to polymorphisms in the endothelial nitric oxide synthase gene (eNOS) might predispose to the disease.


METHODS
We investigated the role of eNOS T-786C, G894T and 4a4b polymorphisms in predisposing to both pre-eclampsia and the recurrence of negative pregnancy events, per se and in the presence of angiotensin-converting enzyme (ACE) DD genotype, and investigated their influence on maternal-fetal flow in 106 non-thrombophilic women with a history of pre-eclampsia, compared with 106 women with a history of normal pregnancy.


RESULTS
No association between eNOS polymorphisms and predisposition to pre-eclampsia was found; nevertheless, the contemporary presence of eNOS 894TT and -786CC genotypes represented a susceptibility factor to the disease. In 48 out of 106 women, documented complications (pre-eclampsia and fetal growth restriction) were present in the current pregnancy. The eNOS 894TT genotype influenced the risk of recurrence of negative events (odds ratio = 5.45), particularly in contemporary women homozygous for both eNOS 894TT and ACE DD genotypes (odds ratio = 11.4). Throughout the pregnancy, a progressive alteration of maternal-fetal flow indices was found in women carrying the eNOS 894TT genotype, and this effect was strengthened in women with the contemporary presence of the ACE DD genotype.


CONCLUSIONS
An original finding is the increased risk of pre-eclampsia and recurrence of pregnancy negative events, probably by modulating the maternal-fetal flow, in women homozygous for the eNOS 894T allele previously analyzed for the ACE I/D polymorphism.
Fatini
Cinzia
C
Department of Medical and Surgical Critical Care, Section of Clinical Medicine and Cardiology, University of Florence, Florence, Italy. cinziafatini@hotmail.com
Sticchi
Elena
E
Gensini
Francesca
F
Genuardi
Maurizio
M
Tondi
Filippo
F
Gensini
Gian Franco
GF
Riviello
Chiara
C
Parretti
Elena
E
Mello
Giorgio
G
Abbate
Rosanna
R
D000328:Adult; D000483:Alleles; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008431:Maternal-Fetal Exchange; D052250:Nitric Oxide Synthase Type III / Q000235:genetics* / Q000502:physiology*; D016017:Odds Ratio; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011110:Polymorphism, Genetic; D011225:Pre-Eclampsia / Q000175:diagnosis* / Q000473:pathology; D011247:Pregnancy; D011256:Pregnancy Outcome; D012008:Recurrence; D019851:Thrombophilia / Q000235:genetics
D052250:Nitric Oxide Synthase Type III; D007703:Peptidyl-Dipeptidase A