A common polymorphism in NR1H2 (LXRbeta) is associated with preeclampsia

<p>Abstract</p> <p>Background</p> <p>Preeclampsia is a frequent complication of pregnancy and a leading cause of perinatal mortality. Both genetic and environmental risk factors have been identified. Lipid metabolism, particularly cholesterol metabolism, is associated with this disease. Liver X receptors alpha (NR1H3, also known as LXRalpha) and beta (NR1H2, also known as LXRbeta) play a key role in lipid metabolism. They belong to the nuclear receptor superfamily and are activated by cholesterol derivatives. They have been implicated in preeclampsia because they modulate trophoblast invasion and regulate the expression of the endoglin (CD105) gene, a marker of preeclampsia. The aim of this study was to investigate associations between the <it>NR1H3 </it>and <it>NR1H2 </it>genes and preeclampsia.</p> <p>Methods</p> <p>We assessed associations between single nucleotide polymorphisms of <it>NR1H3 </it>(rs2279238 and rs7120118) and <it>NR1H2 </it>(rs35463555 and rs2695121) and the disease in 155 individuals with preeclampsia and 305 controls. Genotypes were determined by high-resolution melting analysis. We then used a logistic regression model to analyze the different alleles and genotypes for those polymorphisms as a function of case/control status.</p> <p>Results</p> <p>We found no association between <it>NR1H3 </it>SNPs and the disease, but the <it>NR1H2 </it>polymorphism rs2695121 was found to be strongly associated with preeclampsia (genotype C/C: adjusted odds ratio, 2.05; 95% CI, 1.04-4.05; <it>p </it>= 0.039 and genotype T/C: adjusted odds ratio, 1.85; 95% CI, 1.01-3.42; <it>p </it>= 0.049).</p> <p>Conclusions</p> <p>This study provides the first evidence of an association between the <it>NR1H2 </it>gene and preeclampsia, adding to our understanding of the links between cholesterol metabolism and this disease.</p

Some hemostasis variables at the end of the population distributions are risk factors for severe postpartum hemorrhages.

International audienceBACKGROUND: Severe postpartum hemorrhages (PPH) represent a significant cause of maternal morbidity/mortality, but little is known about its hemostasis-related risk factors. Among the 32 463 women enrolled in the NOHA First cohort, 317 developed severe PPH (S-PPH group), 1269 non-severe PPH (NS-PPH group) and the remaining individuals were considered as control women (C group). METHODS: We performed a case-control study, including 317 triplets of women allocated from the three groups that shared the same clinical characteristics as the S-PPH group. RESULTS: From values obtained 6-9 months after delivery, low (but not-deficient) levels of fibrinogen, von Willebrand factor (VWF) antigen, factor (F) XI, platelet CD42b, TRAP-induced increase of platelet CD41a and high values of serum residual prothrombin activity or closure aperture times using the collagen-ADP cartridge on the PFA-100 system, and blood group O, were independently associated with a significant risk of severe PPH. Being positive for at least two of these eight variables was found in 1.6%, 3.5% and 20.8% of the women from the C, the NS-PPH and the S-PPH groups, respectively, the odds ratio for S-PPH in such a case being 16.4, 95%CI (6.5-41), P < 0.0001. CONCLUSIONS: Women with some hemostasis-related variables at the low or high end of the population distributions are prone to the severe forms of PPH. Clinical trials will allow us to know if acting on these risk factors can lower the clinical severity of PPH