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

BMC Medical Genetics

Research Article

Jean-Paul Brouillet¹  Anne Polge¹  Alexandre Evrard¹  Kevin Mouzat¹  Serge Lumbroso¹  Eric Mercier²  Jean-Christophe Gris²  Jean-Pierre Balducchi³  Silvère Baron⁴ 

[1] Department of Biochemistry, Nimes University Hospital, F-30029, Nîmes Cedex 9, France;Department of Hematology, Nimes University Hospital, F-30029, Nîmes Cedex 9, France;Department of Internal Medicine, Nimes University Hospital, F-30029, Nîmes Cedex 9, France;GReD Laboratory, UMR CNRS 6247 - Clermont University - INSERM U931, F-63177, Aubière Cedex, France;

关键词: Preeclampsia;    Single Nucleotide Polymorphism;    Cholesterol Metabolism;    Trophoblast Invasion;    Splice Site Prediction;   

DOI  :  10.1186/1471-2350-12-145

 received in 2011-05-24, accepted in 2011-10-26,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundPreeclampsia 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 NR1H3 and NR1H2 genes and preeclampsia.MethodsWe 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.ResultsWe 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).ConclusionsThis 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.

【 授权许可】

CC BY   
© Mouzat et al; licensee BioMed Central Ltd. 2011