Abstract | BACKGROUND: METHODS AND FINDINGS: We determined five common mutations in TLR4 (D299G and T399I) and NOD2 (R702W, G908R and L1007fs) in 340 primiparous women with a history of early-onset preeclampsia, of whom 177 women developed HELLP syndrome and in 113 women with a history of only uneventful pregnancies as controls. In addition, we assessed plasma levels of pro-inflammatory biomarkers C-reactive protein, interleukin-6, soluble intercellular adhesion molecule-1, fibrinogen and von Willebrand factor in a subset of 214 women included at least six months after delivery. After adjustment for maternal age and chronic hypertension, attenuating allelic variants of TLR4 were more common in women with a history of early-onset preeclampsia than in controls (OR 2.9 [95% CI 1.2-6.7]). Highest frequencies for TLR4 variants were observed in women who developed HELLP syndrome (adjusted OR 4.1 [95% CI 1.7-9.8]). In addition, high levels of interleukin-6 and fibrinogen were associated with a history of early-onset preeclampsia. Combined positivity for any of the TLR4 and NOD2 allelic variants and high levels of interleukin-6 was 6.9-fold more common in women with a history of early-onset preeclampsia (95% CI 2.1-23.2) compared to controls. CONCLUSIONS: We observed an association of common TLR4 and NOD2 gene variants, and pro-inflammatory phenotype with a history of early-onset preeclampsia and HELLP syndrome. These findings suggest involvement of the maternal innate immune system in severe hypertensive disorders of pregnancy.
|
Authors | Bas B van Rijn, Arie Franx, Eric A P Steegers, Christianne J M de Groot, Rogier M Bertina, Gerard Pasterkamp, Hieronymus A M Voorbij, Hein W Bruinse, Mark Roest |
Journal | PloS one
(PLoS One)
Vol. 3
Issue 4
Pg. e1865
(Apr 02 2008)
ISSN: 1932-6203 [Electronic] United States |
PMID | 18382655
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Endotoxins
- NOD2 protein, human
- Nod2 Signaling Adaptor Protein
- TLR4 protein, human
- Toll-Like Receptor 4
|
Topics |
- Adult
- Alleles
- Endotoxins
(metabolism)
- Female
- Gene Expression Regulation
- Genetic Predisposition to Disease
- Genetic Variation
- HELLP Syndrome
(genetics)
- Humans
- Inflammation
- Models, Biological
- Nod2 Signaling Adaptor Protein
(genetics)
- Pre-Eclampsia
(genetics)
- Pregnancy
- Toll-Like Receptor 4
(genetics)
|