title: Angiotensin converting enzyme intron 16 insertion/deletion genotype is associated with plasma C-reactive protein concentration in uteroplacental dysfunction.
abstract: BACKGROUND
  Disturbance of the uteroplacental circulation (UPC) and the renin-angiotensin system are involved in the pathogenesis of preeclampsia. In women with history of preeclampsia persistently elevated C-reactive protein (CRP) levels have been described. The angiotensin-converting enzyme (ACE) intron 16 insertion/deletion (I/D) genotype is associated with ACE activity and assumed to be a risk factor for preeclampsia. As ACE generates proinflammatory angiotensin II, we analysed, whether ACE intron 16 I/D genotype is associated with CRP and whether this association exhibited a relation to uteroplacental dysfunction.
  
  
  METHODS
  A total of 639 women have been followed during pregnancy with repeated measurements of CRP levels (observations: n=2333). ACE intron 16 I/D genotype was determined, and its association with CRP was assessed with adjustment for non-independent observations.
  
  
  RESULTS
  CRP levels of ACE D allele carriers were significantly higher than those of the ACE II (wild-type) genotype (p=0.0003, p(adj)=0.04). This relation was allele-dose dependent (p<10(-4), p(adj)<0.02). Association between ACE I/D and CRP was significantly restricted to patients presenting with impaired UPC in univariate (p<0.04) and multivariate analyses (p=0.01).
  
  
  CONCLUSIONS
  The ACE I/D genotype is significantly associated with CRP elevations during pregnancies complicated by disturbed UPC. Whether this effect on CRP is involved in pathogenesis of preeclampsia has to be elucidated.
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Häupl
authors.affiliation: Institute of Laboratory Medicine and Pathobiochemistry, Charité-Universitätsmedizin Berlin, Germany Department of Laboratory Medicine & Toxicology, Labor Berlin-Charité Vivantes GmbH, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Zimmermann
authors.affiliation: Institute of Transfusion Medicine, Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kalus
authors.affiliation: Institute of Transfusion Medicine, Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Salih
authors.initials: S
authors.lastname: Yürek
authors.affiliation: Institute of Transfusion Medicine, Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Koscielny
authors.affiliation: Institute of Laboratory Medicine and Pathobiochemistry, Charité-Universitätsmedizin Berlin, Germany Department of Laboratory Medicine & Toxicology, Labor Berlin-Charité Vivantes GmbH, Germany berthold.hoppe@charite.de.
authors.forename: Berthold
authors.initials: B
authors.lastname: Hoppe
mesh_terms: D000328:Adult; D002097:C-Reactive Protein / Q000378:metabolism*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D054643:INDEL Mutation / Q000235:genetics*; D007438:Introns / Q000235:genetics*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D010920:Placenta / Q000503:physiopathology*; D011247:Pregnancy; D014599:Uterus / Q000503:physiopathology*
chemical_list: D002097:C-Reactive Protein; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A
keywords: Angiotensin-converting enzyme; C-reactive protein; genotype; inflammation; uteroplacental circulation