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.


METHODS
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 (p(g)<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).


CONCLUSIONS
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.
Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Brno, Czech Republic. jbienert@med.muni.cz
Julie
J
Bienertova-Vasku
Petr
P
Bienert
Zuzana
Z
Dostalova
Josef
J
Chovanec
Anna
A
Vasku
Vladimir
V
Vasku
D000328:Adult; D000483:Alleles; D054458:Amplified Fragment Length Polymorphism Analysis; D016022:Case-Control Studies; D018153:Czech Republic / Q000453:epidemiology; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006785:Hospitals, University; D006801:Humans; D010044:Outpatient Clinics, Hospital; D020641:Polymorphism, Single Nucleotide; D011225:Pre-Eclampsia / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D011247:Pregnancy; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors
D043884:Receptor, Cannabinoid, CB1