title: Impact of maternal angiotensinogen M235T polymorphism and angiotensin-converting enzyme insertion/deletion polymorphism on blood pressure, protein excretion and fetal outcome in pregnancy.
abstract: OBJECTIVE
  To test the hypothesis that genetically determined alterations of the renin-angiotensin system are associated with hypertensive disorders in pregnancy.
  
  
  METHODS
  A genetic association study was conducted at the obstetrics department of the Charité university hospital, Berlin, Germany. A total of 1068 Caucasian women were consecutively included after delivery and genotyped for the angiotensinogen M235T polymorphism and the angiotensin-converting enzyme (ACE) insertion/deletion polymorphism.
  
  
  RESULTS
  Women homozygous for the angiotensinogen T allele have significantly elevated mean systolic and diastolic blood pressures in the third trimester (118.4 +/- 1.1/71.5 +/- 0.7 versus 116.9 +/- 0.3/70.4 +/- 0.2 mmHg, n = 128 versus 940; P < 0.05). This finding is especially pronounced in the subgroup of primigravid women. The ACE polymorphism is not associated with blood pressure during pregnancy. None of the polymorphisms is associated with urinary protein excretion or oedema during pregnancy. Maternal polymorphisms do not influence fetal growth and birth weight. There is, however, an interesting trend towards an increased incidence of circulatory system malformations in newborns carrying alleles that are known to be associated with decreased intrinsic renin-angiotensin system activity.
  
  
  CONCLUSIONS
  We demonstrate for the first time in a large Caucasian population that a common maternal polymorphism of the angiotensinogen gene is related to a blood pressure increase during pregnancy. The angiotensinogen M235T polymorphism might contribute to the multifactorial pathogenesis of gestational hypertension and pre-eclampsia.
authors.affiliation: Department of Nephrology, Charité Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Thiemo
authors.initials: T
authors.lastname: Pfab
authors.forename: Bulza
authors.initials: B
authors.lastname: Stirnberg
authors.forename: Andreas
authors.initials: A
authors.lastname: Sohn
authors.forename: Katrin
authors.initials: K
authors.lastname: Krause
authors.forename: Torsten
authors.initials: T
authors.lastname: Slowinski
authors.forename: Michael
authors.initials: M
authors.lastname: Godes
authors.forename: Florian
authors.initials: F
authors.lastname: Guthmann
authors.forename: Roland
authors.initials: R
authors.lastname: Wauer
authors.forename: Horst
authors.initials: H
authors.lastname: Halle
authors.forename: Berthold
authors.initials: B
authors.lastname: Hocher
mesh_terms: D019943:Amino Acid Substitution; D000808:Angiotensinogen / Q000235:genetics*; D001794:Blood Pressure / Q000502:physiology*; D016022:Case-Control Studies; D004251:DNA Transposable Elements; D005260:Female; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D007231:Infant, Newborn; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000235:genetics*; D011256:Pregnancy Outcome; D011507:Proteinuria; D017384:Sequence Deletion
chemical_list: D004251:DNA Transposable Elements; D000808:Angiotensinogen; D007703:Peptidyl-Dipeptidase A