Polymorphism of genes associated with the age at menarche and the risk of complications of pregnancy in women in the Central Black Earth Region of Russia
Background: The most common complications of pregnancy associated with metabolic and hemodynamic disorders in the mother-placenta-fetus system are placental insufficiency and preeclampsia. Preeclampsia is one of the leading causes of maternal and perinatal deaths. The aim of the study: To study the role of polymorphism of candidate genes for menarche with the risk of preeclampsia in women of the Central Black Earth region of Russia. Materials and methods: The sample for the study included 997 women: 366 pregnant women with preeclampsia and 631 women in the control group. For the study, polymorphic loci of genes associated with menarche (6 SNPs) were selected: luteinizing hormone / chorionic gonadotropin receptor (rs7579411 and rs4953616 LHCGR), follicle-stimulating hormone receptor (rs6732220 and rs4953654 FSHR) alpha estrogen receptor (rs3020394 and rs1884051 ESR1)). Genotyping of DNA samples was performed using the MALDI method and a MassARRAY Analyzer 4 mass spectrometer («Seqeunom», United States). Associations of SNPs of candidate genes with preeclampsia were assessed using logistic (log-linear) regression according to additive, recessive, and dominant models, adjusted for covariates. To assess the direction of associations of SNPs with preeclampsia, the odds ratio (OR) and its 95% confidence interval (95% CI) were used. Results: It was found that the G allele of rs3020394 ESR1 is associated with the development of preeclampsia in the recessive model (OR = 1.74, 95% Сl 1.06-2.85, p = 0.029). The identified associations of this SNP may be related to its regulatory significance: rs3020394 ESR1 is localized at the site of modified histones in the enhancer regions and at the DNase-hypersensitive site. Conclusion: The G allele of rs3020394 ESR1 is associated with an increased risk of preeclampsia in women from the Central Black Earth Region of Russia (OR = 1.74).