A common variation in the cannabinoid 1 receptor (CNR1) gene is associated with pre-eclampsia in the Central European population

Objective: Recently it has been proposed that tightly regulated levels of endogenous cannabinoids play a fundamental role in early placental development. The aim of this study was to investigate associations of three single-nucleotide polymorphisms (SNPs) in the cannabinoid 1 receptor (CNR1) gene (rs1049353, rs12720071 and rs806368) and their inferred haplotypes with pre-eclampsia, a severe pregnancy-associated condition characterized by abnormal development and remodeling of spiral decidual arteries. Study design: The case-control study comprised a total of 115 pre-eclamptic women and 145 healthy pregnant controls, all originating from the Central-European Czech population. Using PCR-based methods, we tested rs1049353, rs12720071 and rs806368 in the CNR1 gene and haplotypes were constructed. Results: Statistically significant difference in genotype distributions of rs806368 (pg < 10(-3)) was observed when comparing the cases and the controls; the cases presenting with significantly lower proportion of CC homozygotes. In multivariate modeling, the rs806368 served as a predictor for pre-eclampsia development (beta = 0.15; p = 0.04). Haplotype analysis revealed presence of four common haplotypes; the CAA haplotype being less frequent in pre-eclamptic cases compared to the controls (p < 0.008). Analysis of regression models confirmed the independent prediction role of AAC haplotype for pre-eclampsia onset (beta = -0.18; p = 0.03). Conclusion: This is the first study focusing on the relationship between SNPs in the CNR1 gene and pre-eclampsia risk. Although limited by a relatively small sample size, the study indicates that rs806368 in the CNR1 gene may act as a susceptibility marker for pre-eclampsia in humans. (C) 2010 Elsevier Ireland Ltd. All rights reserved.