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

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

Author information

1
Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Germany.
2
Institute of Laboratory Medicine and Pathobiochemistry, Charité-Universitätsmedizin Berlin, Germany Department of Laboratory Medicine & Toxicology, Labor Berlin-Charité Vivantes GmbH, Germany.
3
Institute of Transfusion Medicine, Charité-Universitätsmedizin Berlin, Germany.
4
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.

Abstract

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

PMID:
25155623
DOI:
10.1177/1470320314539181
[Indexed for MEDLINE]

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