Published Online
on March 24, 2003

A more recent version of this article appeared on April 1, 2003

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Submitted on August 21, 2002
Revised on September 16, 2002

Maternal-Fetal Flow, Negative Events, and Preeclampsia. Role of ACE I/D Polymorphism

Giorgio Mello; Elena Parretti; Francesca Gensini; Elena Sticchi; Federico Mecacci; Gianfranco Scarselli; Maurizio Genuardi; Rosanna Abbate^*; and Cinzia Fatini

From the Department of Gynecology, Perinatology, and Human Reproduction (G.M., E.P., F.M., G.S., C.F.), the Department of Physiopathology (E.S., M.G.), Section of Medical Genetics, and the Department of Medical and Surgical Critical Care (R.A., C.F.), Section of Clinical Medicine and Cardiology, University of Florence, Florence, Italy.

^* To whom correspondence should be addressed. E-mail: rosabbate{at}tin.it.

Abstract--The risk for an adverse pregnancy outcome is markedly higher in women with history of preeclampsia. This may stem from impaired placentation in early gestation and from high impedance to flow in uteroplacental circulation. The renin-angiotensin system is one of the mediators of the remodeling of spiral arteries throughout pregnancy. The D allele of the Insertion/Deletion (I/D) polymorphism in the ACE gene has been associated with higher ACE activity, accounting for 47% of the total phenotypic variance of serum enzyme levels. To investigate whether the ACE I/D polymorphism affects maternal uteroplacental and fetal umbilical circulation and the pregnancy outcome in women with a history of preeclampsia, 106 women underwent Doppler examination of uterine arteries resistance index and umbilical artery pulsatility index at the 16th, 20th, and 24th weeks of gestation and were genotyped for the I/D polymorphism. This study found a difference in genotype distribution (P=0.0002) and allele frequency (P<0.0001) between women with and those without preeclampsia recurrence and fetal growth restriction as well as an association (P=0.0007) between DD genotype and risk of recurrent preeclampsia or fetal growth restriction. At the 16th, 20th, and 24th weeks, uterine artery resistance indexes were significantly lower in II, higher in DD, and intermediate in ID genotype carriers, whereas the umbilical artery pulsatility index values were significantly higher in the DD group in comparison to ID and II genotypes. The current study shows that the ACE I/D polymorphism affects uteroplacental and umbilical flows and the recurrence of an adverse pregnancy outcome in women with history of preeclampsia.

Key words: angiotensin-converting enzyme • polymorphism • preeclampsia • pregnancy

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