Maternal and Fetal Genetic Variation in Vitamin D Metabolism and Umbilical Cord Blood 25-Hydroxyvitamin D

Abstract

Context Single nucleotide polymorphisms (SNPs) in vitamin D metabolism pathway genes are associated with circulating 25-hydroxyvitamin D [25(OH)D] in adults. Less is known about the relationships between mother and offspring SNPs and umbilical cord blood 25(OH)D. Objective (1) To undertake a meta-analysis of the relationships of maternal and offspring SNPs in the vitamin D metabolism pathway and cord blood 25(OH)D in pregnant women including novel data; and (2) to examine these relationships in women who received antenatal cholecalciferol supplementation in a clinical trial. Data Sources Novel data analysis from an observational mother-offspring cohort study (Southampton Women’s Survey) and the MAVIDOS double-blind randomised placebo-control trial of 1000 IU/day cholecalciferol supplementation in pregnancy, and an electronic literature search of published studies in PubMed up to 31 July 2021. Study Selection Studies reporting on associations between rs12785878 (DHCR7), rs10741657 (CYP2R1), rs6013897 (CYP24A1) or rs2282679 (GC) and cord blood 25(OH)D. One published study was included in addition to the novel data analysis. Data Synthesis Associations between both maternal and offspring SNPs at rs2282679 (GC) and rs12785878 (DHCR7) and cord blood 25(OH)D were identified. When maternal genotype was adjusted for offspring genotype, and vice versa, there was persisting evidence for associations with maternal rs12785878 (β (95%CI) 1.6nmol/l (0.3, 2.8) per common allele), and offspring rs2282679 (β 3.1nmol/l (2.0, 4.4) per common allele). Maternal and offspring SNPs at rs1074657 and rs613897 were not associated with cord blood 25(OH)D. Conclusions Common genetic variation in the vitamin D metabolism pathway is associated with umbilical cord blood 25(OH)D.

Vitamin D metabolic pathway genes polymorphisms and vitamin D levels in association with neonatal hyperbilirubinemia in China: a single-center retrospective cohort study

“…The rs10877012 is located in the promotor region of the CYP27B1 gene, which might impact transcription and translation processes[ 33 ]. The rs12785878 is located in 8 kilobases upstream from the transcription initiation site of DHCR7 and in an intron of NADSYN1 [ 34 ]. To date, there are no functional studies of the rs12785878, so it remains unclear by which mechanism this SNP influences vitamin D levels and NH risk.…”

Correlation between maternal and umbilical cord 25-hydroxy-vitamin D levels over a range of values. A prospective observational study from the United Arab Emirates

“…Emerging data indicate that genetic factors play a crucial role in the transport and metabolism of vitamin D and its metabolites across the placental barrier but many authors are still referring to the passive transport of 25(OH)D over the placenta [6]. A metanalysis from 2022 investigated the relationship between both maternal and fetal gene variations (Single nucleotide polymorphisms (SNPs)) and UCB 25(OH)D levels and found that common genetic variations are associated with individual levels of 25(OH)D in UCB [7]. Vitamin D is introduced to organ cells after endocytosis and is either bound to vitamin-D-binding protein or is albuminbound [38][39][40].…”

“…Maternal 1,25 (OH)D 2 is thought not to pass the placenta. Fascinating new and upcoming data from epigenetic studies shows that placental functionality and epigenetics dictate the fetal supply of 25 (OH)D's active metabolite, why it is remarkable that many authors still refer to passive transport [6][7][8]. Simple descriptive studies show a moderate to strong correlation between maternal and UCB 25(OH)D to no correlation if the mother is deficient and the ratio is seldom described as negative.…”

“…Simple descriptive studies show a moderate to strong correlation between maternal and UCB 25(OH)D to no correlation if the mother is deficient and the ratio is seldom described as negative. This can either be due to a complex pathway between the mother and the fetus or, more simply, the design of the studies [7,[9][10][11]. There are studies suggesting that maternal diabetes, risk for preeclampsia, delivery of a small for gestational age neonate, preterm rupture of membranes, and dystocia are associated with low vitamin D but according to the Cochrane review from 2019 more studies are needed to prove the evidence for any of these associations [12][13][14].…”

Does antenatal cholecalciferol supplementation affect the mode or timing of delivery? Post hoc analyses of the MAVIDOS randomized controlled trial

“…As these are hypothesis-generating post hoc analyses, and the reasons for operative delivery were not documented, future trials would need to focus on delivery characteristics, such as labour timings, use and reasons for any intervention and analgesia, both to confirm our findings and attempt to elucidate the underlying mechanisms. Future studies should additionally aim to establish the benefits of vitamin D supplementation on these outcomes in specific risk groups for both vitamin D deficiency (for example, obesity, prolonged hospital admission or Black, Asian and Minority Ethnic groups) and adverse obstetric outcomes, and with randomization stratified by factors associated with the biochemical response to vitamin D supplementation [63][64][65] and risk of poor labour outcomes.…”