No abstract

For the first time in the Polish population, we aimed to investigate associations between the VDR gene single-nucleotide polymorphisms (SNPs) BsmI (rs15444410), ApaI (rs7975232), FokI (rs19735810), and TaqI (rs731236) and the development of preeclampsia (PE). A case–control study surveyed 122 preeclamptic and 184 normotensive pregnant women. The polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) method was performed to examine the maternal VDR FokI, BsmI, TaqI, and ApaI polymorphisms. The VDR BsmIAA homozygous genotype was statistically significantly more frequent in preeclamptic women compared to the control group (p = 0.0263), which was also associated with a 2-fold increased risk of PE (OR = 2.06, p = 0.012). A correlation between the VDR BsmI polymorphism with systolic and diastolic blood hypertension was noted. Furthermore, 3-marker haplotype CTA (TaqI/ApaI/BsmI) was associated with significantly higher systolic (p = 0.0075) and diastolic (p = 0.0072) blood pressure. Association and haplotype analysis indicated that the VDR BsmI A allele could play a significant role in the PE pathomechanism and hence could be a risk factor for PE development in pregnant Polish women. These results indicate the importance of the VDR BsmI polymorphism and reveal that this variant is closely associated with a higher predisposition to hypertension.

Vitamin D3 (VD3) and its steroidal nuclear receptor are necessary for proper development of a pregnancy. They play a key role in implantation, modulate the mother's immune response to the developing fetus, influence the final development of a placenta, and regulate blood pressure and glucose tolerance. VD3 deficiency can lead to the occurrence of obstetric complications such as recurrent miscarriages, preeclampsia, intrauterine growth restriction, gestational diabetes and preterm labor. VD3 deficiency is a common phenomenon across the globe; because of the higher demand placed on their bodies, pregnant women are more likely to develop VD3 deficiency. During pregnancy, VD3 supplementation is a safe method of treatment without risk of side effects or intoxication. To obtain the greatest efficacy, VD3 supplementation should start at the pregnancy planning stage, under control of the VD3 serum concentration, which should exceed 30 ng/mL (75 nmol/L); this is to start the positive effect of the optimal VD3 concentration from the beginning of a pregnancy.

(1) Background: Considerable evidence indicates that the occurrence of preeclampsia (PE) is associated with a reduced vitamin D (VD) level. Several studies have found that VD deficiency is correlated with disturbed trophoblast invasion, reduced angiogenesis and increased vasoconstriction. Because the vitamin D receptor (VDR) and CYP27B1 and CYP2R1 hydrolases are strongly involved in VD metabolism, the goal of the present study was to evaluate their genes and proteins expression in the placentas from preeclamptic women. (2) Methods: Samples and clinical data were obtained from 100 Polish women (41 women with preeclampsia and 59 healthy pregnant controls). The whole PE group was divided into subgroups according to gestation week of pregnancy ending before and after 34 gestational weeks (early/late-onset preeclampsia (EOPE/LOPE)). However, finally, to reduce confounding by differences in gestational age, the EOPE group was excluded from the analysis of mRNA and protein placental expression, and we focus on the comparison between LOPE and control groups. The placental VDR, CYP27B1 and CYP2R1 mRNA expression was analyzed using RT-PCR, and placental protein levels were determined by ELISA assay. (3) Results. (3.1) Placental gene expression: Expression levels of both genes, CYP27B1 (1.17 vs. 1.05 in controls, p = 0.006) and CYP2R1 (2.01 vs. 1.89 in controls, p = 0.039), were significantly higher in preeclamptic placentas than in the control group. Interestingly, VDR expression was significantly lower in placentas from the PE group (1.15 vs. 1.20 in controls, p = 0.030). After dividing all preeclamptic women into subgroups only for the CYP27B1 gene, a significantly higher placental expression in the LOPE subgroup than the healthy controls was observed (padj = 0.038). (3.2) Placental protein expression: The results revealed that protein expression levels of CYP27B1 in the preeclamptic group were similar (5.32 vs. 5.23 in controls, p = 0.530). There was a significant difference in median VDR and CYP2R1 protein levels between studied groups (VDR: 2.56 vs. 3.32 in controls, p < 0.001; CYP2R1: 1.32 vs. 1.43 in controls, p = 0.019). After stratification of preeclamptic women into subgroups, a significant difference was observed only in the VDR protein level. The medians in the LOPE subgroups were significantly lower compared to the healthy control group. In the whole study group, the placental VDR protein level was inversely correlated with systolic and diastolic blood pressure (all p < 0.001), and positively correlated with gestational age (p < 0.001) and infant birth weight (p = 0.014). (4) Conclusions: Lower mRNA and protein expression of VDR in preeclamptic placentas, and also VDR protein expression, could play a pivotal role in preeclampsia development. Additionally, the higher mRNA expression of both CYP27B1 and CYP2R1 hydrolase genes in placentas from preeclamptic women could indicate the compensatory role of these enzymes in preeclampsia etiology. Our results also indicate that placental VDR protein level could be one of the factors modulating blood pressure in pregnant women, as well as influencing gestational age and infant birth weight. Considering the importance of these findings, future studies are warranted.