Search for an association between V249I and T280M CX3CR1 genetic polymorphisms, endothelial injury and preeclampsia: the ECLAXIR study.

<h4>Background</h4>Preeclampsia and coronary-artery disease share risk factors, suggesting common pathophysiological mechanisms. CX3CR1/CX3CL1 mediates leukocyte migration and adhesion and has been implicated in the pathophysiology of several inflammatory diseases. M280/I249 variants of...

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Autores principales: Alain Stepanian, Soraya Benchenni, Tiphaine Beillat-Lucas, Sophie Omnes, Fannie Defay, Edith Peynaud-Debayle, Gabriel Baron, Agnès Le Querrec, Michel Dreyfus, Laurence Salomon, Vassilis Tsatsaris, Dominique de Prost, Laurent Mandelbrot, ECLAXIR study group
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Publicado: Public Library of Science (PLoS) 2009
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spelling oai:doaj.org-article:afc7d0bf34854e6daef6d618b7dd96452021-11-25T06:21:42ZSearch for an association between V249I and T280M CX3CR1 genetic polymorphisms, endothelial injury and preeclampsia: the ECLAXIR study.1932-620310.1371/journal.pone.0006192https://doaj.org/article/afc7d0bf34854e6daef6d618b7dd96452009-07-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19587779/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Preeclampsia and coronary-artery disease share risk factors, suggesting common pathophysiological mechanisms. CX3CR1/CX3CL1 mediates leukocyte migration and adhesion and has been implicated in the pathophysiology of several inflammatory diseases. M280/I249 variants of CX3CR1 are associated with an atheroprotective effect and reduced endothelial dysfunction. The aim of this study was to search for an association between V249I and T280M polymorphisms of CX3CR1, preeclampsia and endothelial dysfunction.<h4>Methodology/principal findings</h4>We explored these polymorphisms with real-time polymerase chain reaction in a case-control study (184 white women with preeclampsia and 184 matched normotensive pregnant women). Endothelial dysfunction biomarkers including von Willebrand factor, VCAM-1 and thrombomodulin, as well as the soluble form of CX3CL1 were measured by enzyme-linked immunosorbent assays (ELISA). The I249 and M280 alleles were associated neither with preeclampsia, nor with its more severe form or with endothelial injury. In contrast, we found a trend toward increased CX3CL1 levels in preeclampsia patients, especially in early-onset- preeclampsia as compared to its level in later-onset- preeclampsia.<h4>Conclusions/significance</h4>This is the first study to characterize the CX3CR1 gene polymorphisms in patients with preeclampsia. We found no differences in genotype or haplotype frequencies between patients with PE and normal pregnancies, suggesting that maternal CX3CR1 V249I and T280M polymorphisms do not increase susceptibility to preeclampsia. Further studies should be performed to directly evaluate the pathophysiological role of CX3CL1, a molecule abundantly expressed in endometrium, which has been shown to stimulate human trophoblast migration.Alain StepanianSoraya BenchenniTiphaine Beillat-LucasSophie OmnesFannie DefayEdith Peynaud-DebayleGabriel BaronAgnès Le QuerrecMichel DreyfusLaurence SalomonVassilis TsatsarisDominique de ProstLaurent MandelbrotECLAXIR study groupPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 7, p e6192 (2009)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Alain Stepanian
Soraya Benchenni
Tiphaine Beillat-Lucas
Sophie Omnes
Fannie Defay
Edith Peynaud-Debayle
Gabriel Baron
Agnès Le Querrec
Michel Dreyfus
Laurence Salomon
Vassilis Tsatsaris
Dominique de Prost
Laurent Mandelbrot
ECLAXIR study group
Search for an association between V249I and T280M CX3CR1 genetic polymorphisms, endothelial injury and preeclampsia: the ECLAXIR study.
description <h4>Background</h4>Preeclampsia and coronary-artery disease share risk factors, suggesting common pathophysiological mechanisms. CX3CR1/CX3CL1 mediates leukocyte migration and adhesion and has been implicated in the pathophysiology of several inflammatory diseases. M280/I249 variants of CX3CR1 are associated with an atheroprotective effect and reduced endothelial dysfunction. The aim of this study was to search for an association between V249I and T280M polymorphisms of CX3CR1, preeclampsia and endothelial dysfunction.<h4>Methodology/principal findings</h4>We explored these polymorphisms with real-time polymerase chain reaction in a case-control study (184 white women with preeclampsia and 184 matched normotensive pregnant women). Endothelial dysfunction biomarkers including von Willebrand factor, VCAM-1 and thrombomodulin, as well as the soluble form of CX3CL1 were measured by enzyme-linked immunosorbent assays (ELISA). The I249 and M280 alleles were associated neither with preeclampsia, nor with its more severe form or with endothelial injury. In contrast, we found a trend toward increased CX3CL1 levels in preeclampsia patients, especially in early-onset- preeclampsia as compared to its level in later-onset- preeclampsia.<h4>Conclusions/significance</h4>This is the first study to characterize the CX3CR1 gene polymorphisms in patients with preeclampsia. We found no differences in genotype or haplotype frequencies between patients with PE and normal pregnancies, suggesting that maternal CX3CR1 V249I and T280M polymorphisms do not increase susceptibility to preeclampsia. Further studies should be performed to directly evaluate the pathophysiological role of CX3CL1, a molecule abundantly expressed in endometrium, which has been shown to stimulate human trophoblast migration.
format article
author Alain Stepanian
Soraya Benchenni
Tiphaine Beillat-Lucas
Sophie Omnes
Fannie Defay
Edith Peynaud-Debayle
Gabriel Baron
Agnès Le Querrec
Michel Dreyfus
Laurence Salomon
Vassilis Tsatsaris
Dominique de Prost
Laurent Mandelbrot
ECLAXIR study group
author_facet Alain Stepanian
Soraya Benchenni
Tiphaine Beillat-Lucas
Sophie Omnes
Fannie Defay
Edith Peynaud-Debayle
Gabriel Baron
Agnès Le Querrec
Michel Dreyfus
Laurence Salomon
Vassilis Tsatsaris
Dominique de Prost
Laurent Mandelbrot
ECLAXIR study group
author_sort Alain Stepanian
title Search for an association between V249I and T280M CX3CR1 genetic polymorphisms, endothelial injury and preeclampsia: the ECLAXIR study.
title_short Search for an association between V249I and T280M CX3CR1 genetic polymorphisms, endothelial injury and preeclampsia: the ECLAXIR study.
title_full Search for an association between V249I and T280M CX3CR1 genetic polymorphisms, endothelial injury and preeclampsia: the ECLAXIR study.
title_fullStr Search for an association between V249I and T280M CX3CR1 genetic polymorphisms, endothelial injury and preeclampsia: the ECLAXIR study.
title_full_unstemmed Search for an association between V249I and T280M CX3CR1 genetic polymorphisms, endothelial injury and preeclampsia: the ECLAXIR study.
title_sort search for an association between v249i and t280m cx3cr1 genetic polymorphisms, endothelial injury and preeclampsia: the eclaxir study.
publisher Public Library of Science (PLoS)
publishDate 2009
url https://doaj.org/article/afc7d0bf34854e6daef6d618b7dd9645
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