Association between vitamin D plasma concentrations and VDR gene variants and the risk of premature birth

Dutra, Letícia Veríssimo; Affonso-Kaufman, Fernando Alves; Cafeo, Fernanda Ramirez; Kassai, Milene Saori; Barbosa, Caio Parente; Figueiredo, Francisco Winter dos Santos; Souza, Fabíola Isabel Suano de; Bianco, Bianca

doi:10.1186/s12884-019-2671-2

Cited by 20 publications

(12 citation statements)

References 46 publications

(68 reference statements)

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“…These discrepancies could arise due to the methods of measuring vitamin D and the myriad of confounding variables among the observational studies, including ethnicities and baseline 25(OH)D levels of the subjects [40]. Other researchers found that vitamin D receptor also plays an important role in determining maternal and neonatal health [41,42]. Vitamin D receptor polymorphisms related to FokI, ApaI, and TaqI were reported to be associated with gestational diabetes mellitus, pre-preeclampsia, and preterm birth (reviewed in [43]).…”

Section: Discussionmentioning

confidence: 99%

Is First Trimester Maternal 25-Hydroxyvitamin D Level Related to Adverse Maternal and Neonatal Pregnancy Outcomes? A Prospective Cohort Study among Malaysian Women

Aziz

Yazid

Rahman

et al. 2020

IJERPH

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Information on the role of 25-hydroxyvitamin D (25(OH)D) in preventing adverse pregnancy/neonatal outcomes is limited in Malaysia. This study aims to determine the relationship between the level of maternal 25(OH)D in the first trimester of pregnant women and their pregnancy/neonatal outcomes. A total of 60 pregnant women in the first trimester were recruited and followed until the end of their pregnancy. The occurrence of any antenatal, delivery, and neonatal complications was recorded. Their blood was collected in the first trimester for total serum 25(OH)D determination using enzyme-linked immunosorbent assay. Overall, 10% of the women had vitamin D deficiency, while 57% had vitamin D insufficiency in their first trimester. No statistically significant difference in 25(OH)D level/status was observed between women with or without antenatal and delivery complications (p > 0.05). No difference in maternal serum 25(OH)D level and vitamin D status was observed between neonates with or without complications (p > 0.05). In conclusion, there is a high prevalence of vitamin D insufficiency among Malaysian pregnant women, but it is not associated with adverse maternal and neonatal outcomes. More comprehensive studies should be planned to verify this relationship.

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Section: Discussionmentioning

confidence: 99%

Is First Trimester Maternal 25-Hydroxyvitamin D Level Related to Adverse Maternal and Neonatal Pregnancy Outcomes? A Prospective Cohort Study among Malaysian Women

Aziz

Yazid

Rahman

et al. 2020

IJERPH

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“…Among the most frequently examined VDR gene variants (FokI, rs2228570; ApaI rs7975232; Bsml rs1544410; TaqI, rs 731236), ApaI, BsmI, and TaqI genotype are in linkage disequilibrium in Caucasian populations ( Knabl et al, 2017 ). In several studies these VDR SNPs increased the risk of preterm birth ( Rosenfeld et al, 2017 ; Dutra et al, 2019 ). As determined in a meta-analysis, the here investigated VDR polymorphism (syn.…”

Section: Discussionmentioning

confidence: 99%

Gene Variants Determine Placental Transfer of Perfluoroalkyl Substances (PFAS), Mercury (Hg) and Lead (Pb), and Birth Outcome: Findings From the UmMuKi Bratislava-Vienna Study

Gundacker

Graf-Rohrmeister²,

Genčík³

et al. 2021

Front. Genet.

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Prenatal exposure to perfluoroalkyl substances (PFAS), bisphenol A (BPA), lead (Pb), total mercury (THg), and methylmercury (MeHg) can affect fetal development. Factors influencing placental transfer rate of these toxins are poorly investigated. Whether prenatal exposure to pollutants has an effect on birth weight is incompletely understood. We therefore aimed (1) to determine placental transfer rates of PFAS, BPA, Pb, THg, and MeHg, (2) to analyze relationships between fetal exposure and birth outcome and (3) to analyze gene variants as mediators of placental transfer rates and birth outcome. Two hundred healthy pregnant women and their newborns participated in the study. BPA, 16 PFAS, THg, MeHg, and Pb were determined using HPLCMS/MS (BPA, PFAS), HPLC-CV-ICPMS (MeHg), CV-AFS (THg), and GF-AAS (Pb). Questionnaires and medical records were used to survey exposure sources and birth outcome. 20 single nucleotide polymorphisms and two deletion polymorphisms were determined by real-time PCR from both maternal and newborn blood. Genotype-phenotype associations were analyzed by categorical regression and logistic regression analysis. Specific gene variants were associated with altered placental transfer of PFAS (ALAD Lys59Asn, ABCG2 Gln141Lys), THg (UGT Tyr85Asp, GSTT1del, ABCC1 rs246221) and Pb (GSTP1 Ala114Val). A certain combination of three gene polymorphisms (ABCC1 rs246221, GCLM rs41303970, HFE His63Asp) was over-represented in newborns small for gestational age. 36% of Austrian and 75% of Slovakian mothers had levels exceeding the HBM guidance value I (2 μg/L) of the German HBM Commission for PFOA. 13% of newborns and 39% of women had Ery-Pb levels above 24 μg/kg, an approximation for the BMDL01 of 12 μg/L set by the European Food Safety Authority (EFSA). Our findings point to the need to minimize perinatal exposures to protect fetal health, especially those genetically predisposed to increased transplacental exposure.

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“…Budhwar et al reported that VD deficiency disturbed homeostasis of the inflammatory response in the placenta, activating the cytokine network and followed by spontaneous premature preterm delivery [57]. At the same time, Dutra et al observed a correlation between maternal VD levels and VDR gene polymorphisms, as well as the risk of premature birth [58]. No less interesting was the observation that maternal VD serum level was associated with infant birthweight among both white and black women [59,60].…”

Section: Vdr Protein Level In Placentasmentioning

confidence: 99%

Placental mRNA and Protein Expression of VDR, CYP27B1 and CYP2R1 Genes Related to Vitamin D Metabolism in Preeclamptic Women

et al. 2021

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(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.

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Association between vitamin D plasma concentrations and VDR gene variants and the risk of premature birth

Cited by 20 publications

References 46 publications

Is First Trimester Maternal 25-Hydroxyvitamin D Level Related to Adverse Maternal and Neonatal Pregnancy Outcomes? A Prospective Cohort Study among Malaysian Women

Is First Trimester Maternal 25-Hydroxyvitamin D Level Related to Adverse Maternal and Neonatal Pregnancy Outcomes? A Prospective Cohort Study among Malaysian Women

Gene Variants Determine Placental Transfer of Perfluoroalkyl Substances (PFAS), Mercury (Hg) and Lead (Pb), and Birth Outcome: Findings From the UmMuKi Bratislava-Vienna Study

Placental mRNA and Protein Expression of VDR, CYP27B1 and CYP2R1 Genes Related to Vitamin D Metabolism in Preeclamptic Women

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