Angiotensin converting enzyme intron 16 insertion/deletion genotype is associated with plasma C-reactive protein concentration in uteroplacental dysfunction

J Renin Angiotensin Aldosterone Syst. 2015 Jun;16(2):422-7. doi: 10.1177/1470320314539181. Epub 2014 Aug 25.


Introduction: 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.

Materials and 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.

Keywords: Angiotensin-converting enzyme; C-reactive protein; genotype; inflammation; uteroplacental circulation.

MeSH terms

  • Adult
  • C-Reactive Protein / metabolism*
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Humans
  • INDEL Mutation / genetics*
  • Introns / genetics*
  • Peptidyl-Dipeptidase A / genetics*
  • Placenta / physiopathology*
  • Pregnancy
  • Uterus / physiopathology*


  • C-Reactive Protein
  • ACE protein, human
  • Peptidyl-Dipeptidase A