Document Detail

Maternal and fetal angiotensinogen gene allele sharing in pre-eclampsia.
MedLine Citation:
PMID:  10426644     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: To compare the angiotensinogen genotypes in normotensive and pre-eclamptic pregnancies in maternal and fetal samples. DESIGN: Prospective observational study. SETTING: University Hospital, Queen's Medical Centre, Nottingham. POPULATION: Forty-three women with pre-eclampsia and 84 normotensive pregnant women. Fetal samples were available for genotyping from 96% of the pregnancies. METHODS: Maternal and fetal DNA was genotyped at angiotensinogen codon 235 and at a dinucleotide repeat polymorphism in the 3' flanking region of the gene. Angiotensinogen and renin concentrations were measured in maternal plasma by radioimmunoassay. RESULTS: In contrast to earlier studies, no association was demonstrated between the angiotensinogen 235 Thr variant and pre-eclampsia. Normotensive pregnant women homozygous for this variant had significantly lower plasma angiotensinogen concentrations (median 2.2 ng AI/mL; IQR 1.8-3.0) than women homozygous for the 235 Met allele (3.6 ng AI/mL; IQR 2.5-4.1; P = 0.04). In pre-eclamptic pregnancies, 79% (11/14) of mothers heterozygous for the dinucleotide repeat allele designated A9 transmitted this allele to the fetus, more frequently than would be expected by chance (P = 0.02). The A9 allele was associated with low plasma angiotensinogen concentrations (P = 0.001) and high renin concentrations (P = 0.02) in normotensive women. CONCLUSIONS: There is no evidence that the angiotensinogen 235 Thr allele is associated with pre-eclampsia in the Nottingham population. The angiotensinogen 235 Thr allele is associated with low plasma angiotensinogen concentrations in normotensive pregnant women, in contrast to the high levels associated with this variant in non-pregnant women, suggesting that regulation of angiotensinogen expression in normal pregnancy may differ significantly from that in the non-pregnant state. There is preliminary evidence that maternal-fetal transmission of an angiotensinogen allele associated with low plasma angiotensinogen concentrations is associated with pre-eclampsia. Impaired generation of angiotensin II at the maternal-fetal interface may be a factor in the pathogenesis of pre-eclampsia.
L Morgan; S Crawshaw; P N Baker; F Broughton Pipkin; N Kalsheker
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of obstetrics and gynaecology     Volume:  106     ISSN:  0306-5456     ISO Abbreviation:  Br J Obstet Gynaecol     Publication Date:  1999 Mar 
Date Detail:
Created Date:  1999-08-11     Completed Date:  1999-08-11     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7503752     Medline TA:  Br J Obstet Gynaecol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  244-51     Citation Subset:  AIM; IM    
Department of Clinical Laboratory Sciences, University Hospital, Nottingham, UK.
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MeSH Terms
Angiotensinogen / blood,  genetics*
Fetal Blood / metabolism*
Polymorphism, Genetic
Pre-Eclampsia / blood,  genetics*
Prospective Studies
Renin / blood
Reg. No./Substance:
11002-13-4/Angiotensinogen; EC

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