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

• Published in: European journal of obstetrics & gynecology and reproductive biology Vol. 155; no. 1; pp. 19 - 22
• Main Authors: Bienertova-Vasku, Julie, Bienert, Petr, Dostalova, Zuzana, Chovanec, Josef, Vasku, Anna, Vasku, Vladimir
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 01.03.2011; Elsevier
• Subjects: Adult; Alleles; Amplified Fragment Length Polymorphism Analysis; Arteries; Biological and medical sciences; Cannabinoids; Case-Control Studies; CNR1; Czech Republic - epidemiology; decidua; Diseases of mother, fetus and pregnancy; Endocannabinoids; Female; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Gynecology; Gynecology. Andrology. Obstetrics; Haplotype; Haplotypes; Homozygotes; Hospitals, University; Humans; Medical sciences; Obstetrics; Obstetrics and Gynecology; Outpatient Clinics, Hospital; Placenta; Polymorphism; Polymorphism, Single Nucleotide; Pre-eclampsia; Pre-Eclampsia - epidemiology; Pre-Eclampsia - genetics; Pre-Eclampsia - metabolism; Pregnancy; Pregnancy. Fetus. Placenta; Receptor, Cannabinoid, CB1 - genetics; Receptor, Cannabinoid, CB1 - metabolism; Regression analysis; Risk Factors; Single-nucleotide polymorphism; Statistical analysis; Europe; Czech Republic; Pre-eclampsia; CNR1; Haplotype; Endocannabinoids; Polymorphism; Pregnancy disorders; Gynecology; Cannabinoid; Obstetrics; Pregnancy toxemia; Gene; Preeclampsia; Public health
• ISSN: 0301-2115; 1872-7654
• DOI: 10.1016/j.ejogrb.2010.11.004

Abstract 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 ( β = 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 ( β = −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.