Angiotensin-converting enzyme I/D polymorphism and preeclampsia risk: evidence of small-study bias.
<h4>Background</h4>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...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2006-12-01
|
| Series: | PLoS Medicine |
| Online Access: | https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.0030520&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850240710686539776 |
|---|---|
| author | Norma C Serrano Luis A Díaz Maria C Páez Clara M Mesa Rodrigo Cifuentes Alvaro Monterrosa Adriana González Liam Smeeth Aroon D Hingorani Juan P Casas |
| author_facet | Norma C Serrano Luis A Díaz Maria C Páez Clara M Mesa Rodrigo Cifuentes Alvaro Monterrosa Adriana González Liam Smeeth Aroon D Hingorani Juan P Casas |
| author_sort | Norma C Serrano |
| collection | DOAJ |
| description | <h4>Background</h4>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.<h4>Methods and findings</h4>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% CI, 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 meta-analysis (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.<h4>Conclusions</h4>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. |
| format | Article |
| id | doaj-art-fe4de60d8e0449d3aae7d7dbe016cb32 |
| institution | OA Journals |
| issn | 1549-1277 1549-1676 |
| language | English |
| publishDate | 2006-12-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Medicine |
| spelling | doaj-art-fe4de60d8e0449d3aae7d7dbe016cb322025-08-20T02:00:47ZengPublic Library of Science (PLoS)PLoS Medicine1549-12771549-16762006-12-01312e52010.1371/journal.pmed.0030520Angiotensin-converting enzyme I/D polymorphism and preeclampsia risk: evidence of small-study bias.Norma C SerranoLuis A DíazMaria C PáezClara M MesaRodrigo CifuentesAlvaro MonterrosaAdriana GonzálezLiam SmeethAroon D HingoraniJuan P Casas<h4>Background</h4>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.<h4>Methods and findings</h4>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% CI, 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 meta-analysis (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.<h4>Conclusions</h4>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.https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.0030520&type=printable |
| spellingShingle | Norma C Serrano Luis A Díaz Maria C Páez Clara M Mesa Rodrigo Cifuentes Alvaro Monterrosa Adriana González Liam Smeeth Aroon D Hingorani Juan P Casas Angiotensin-converting enzyme I/D polymorphism and preeclampsia risk: evidence of small-study bias. PLoS Medicine |
| title | Angiotensin-converting enzyme I/D polymorphism and preeclampsia risk: evidence of small-study bias. |
| title_full | Angiotensin-converting enzyme I/D polymorphism and preeclampsia risk: evidence of small-study bias. |
| title_fullStr | Angiotensin-converting enzyme I/D polymorphism and preeclampsia risk: evidence of small-study bias. |
| title_full_unstemmed | Angiotensin-converting enzyme I/D polymorphism and preeclampsia risk: evidence of small-study bias. |
| title_short | Angiotensin-converting enzyme I/D polymorphism and preeclampsia risk: evidence of small-study bias. |
| title_sort | angiotensin converting enzyme i d polymorphism and preeclampsia risk evidence of small study bias |
| url | https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.0030520&type=printable |
| work_keys_str_mv | AT normacserrano angiotensinconvertingenzymeidpolymorphismandpreeclampsiariskevidenceofsmallstudybias AT luisadiaz angiotensinconvertingenzymeidpolymorphismandpreeclampsiariskevidenceofsmallstudybias AT mariacpaez angiotensinconvertingenzymeidpolymorphismandpreeclampsiariskevidenceofsmallstudybias AT clarammesa angiotensinconvertingenzymeidpolymorphismandpreeclampsiariskevidenceofsmallstudybias AT rodrigocifuentes angiotensinconvertingenzymeidpolymorphismandpreeclampsiariskevidenceofsmallstudybias AT alvaromonterrosa angiotensinconvertingenzymeidpolymorphismandpreeclampsiariskevidenceofsmallstudybias AT adrianagonzalez angiotensinconvertingenzymeidpolymorphismandpreeclampsiariskevidenceofsmallstudybias AT liamsmeeth angiotensinconvertingenzymeidpolymorphismandpreeclampsiariskevidenceofsmallstudybias AT aroondhingorani angiotensinconvertingenzymeidpolymorphismandpreeclampsiariskevidenceofsmallstudybias AT juanpcasas angiotensinconvertingenzymeidpolymorphismandpreeclampsiariskevidenceofsmallstudybias |