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

We assessed associations between single nucleotide polymorphisms of NR1H3 (rs2279238 and rs7120118) and NR1H2 (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.We found no association between NR1H3 SNPs and the disease, but the NR1H2 polymorphism rs2695121 was found to be strongly associated with preeclampsia (genotype C/C: adjusted odds ratio, 2.05; 95% CI, 1.04-4.05; p = 0.039 and genotype T/C: adjusted odds ratio, 1.85; 95% CI, 1.01-3.42; p = 0.049).This study provides the first evidence of an association between the NR1H2 gene and preeclampsia, adding to our understanding of the links between cholesterol metabolism and this disease.Preeclampsia (PE) is a frequent complication of the second half of pregnancy and is one of the leading causes of maternal perinatal mortality and morbidity [1]. This condition, affecting 2.5 to 3% of pregnant women is defined by gestational hypertension accompanied by proteinuria [2,3]. Many risk factors have been described, including, in particular, cardiovascular risks, such as diabetes mellitus and high body mass index [4,5]. Cholesterol metabolism may also contribute to the pathogenesis of preeclampsia. Indeed, high total cholesterol and LDL (low density lipoprotein)-cholesterol levels are significantly associated with this disease [6]. Moreover, it has been shown that a familial history of PE almost triples the risk of a woman developing this disease, consistent with the involvement of genetic factors [4]. Many risk factors have been described, but the molecular mechanisms underlying this disease remain unclear. Liver X receptors (LXRs) NR1H3 and NR1H2, more commonly known as LXRalpha and LXRbeta, play a key role in cholesterol metabolism [7,8]. They belong to a subclass of