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Angiotensin-converting enzyme I/D polymorphism and preeclampsia risk: Evidence of small-study bias

Serrano, NC; Diaz, LA; Paez, MC; Mesa, CM; Cifuentes, R; Monterrosa, A; Gonzalez, A; ... Casas, JP; + view all (2006) Angiotensin-converting enzyme I/D polymorphism and preeclampsia risk: Evidence of small-study bias. PLoS Medicine , 3 (12) , Article e520. 10.1371/journal.pmed.0030520. Green open access

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Abstract

Background Inappropriate activation of the renin-angiotensin system may play a part in the development of preeclampsia. An insertion/deletion polymorphism within the angiotensin-I converting enzyme gene (ACE-I/D) has shown to be reliably associated with differences in angiotensin-converting enzyme (ACE) activity. However, previous studies of the ACE-I/D variant and preeclampsia have been individually underpowered to detect plausible genotypic risks.Methods and Findings A prospective case-control study was conducted in 1,711 unrelated young pregnant women (665 preeclamptic and 1,046 healthy pregnant controls) recruited from five Colombian cities. Maternal blood was obtained to genotype for the ACE-I/D polymorphism. Crude and adjusted odds ratio (OR) and 95% confidence interval (CI) using logistic regression models were obtained to evaluate the strength of the association between ACE-I/D variant and preeclampsia risk. A meta-analysis was then undertaken of all published studies to February 2006 evaluating the ACE-I/D variant in preeclampsia. An additive model (per-D-allele) revealed a null association between the ACE-I/D variant and preeclampsia risk (crude OR 0.95 [ 95% Cl, 0.81-1.10]) in the new case-control study. Similar results were obtained after adjusting for confounders (adjusted per-allele OR 0.90 [ 95% CI, 0.77-1.06]) and using other genetic models of inheritance. A metaanalysis (2,596 cases and 3,828 controls from 22 studies) showed a per-allele OR of 1.26 (95% CI, 1.07-1.49). An analysis stratified by study size showed an attenuated OR toward the null as study size increased.Conclusions It is highly likely that the observed small nominal increase in risk of preeclampsia associated with the ACE D-allele is due to small-study bias, similar to that observed in cardiovascular disease. Reliable assessment of the origins of preeclampsia using a genetic approach may require the establishment of a collaborating consortium to generate a dataset of adequate size.

Type: Article
Title: Angiotensin-converting enzyme I/D polymorphism and preeclampsia risk: Evidence of small-study bias
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pmed.0030520
Publisher version: http://dx.doi.org/10.1371/journal.pmed.0030520
Language: English
Additional information: © 2006 Serrano et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: Insertion-deletion polymorphism, Gene polymorphism, Randomized-trials, Pregnant-women, Vitamin-C, Hypertension, Association, Metaanalysis, Disease, Classification
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics
URI: https://discovery.ucl.ac.uk/id/eprint/118168
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