Maternal vitamin D predominates over genetic factors in determining neonatal circulating vitamin D concentrations 1 – 3

Background: There are multiple potential regulators of neonatal vitamin D status of environmental, genetic, and epigenetic origins. The relation between these factors and circulating neonatal vitamin D has yet to be fully characterized. Objective: The aim of this study was to examine the relative contribution of genetic factors, maternal circulating 25-hydroxyvitamin D [25(OH)D] concentrations, and the placental methylation level of the gene that encodes the primary catabolic enzyme of active vitamin D [25(OH)D-24-hydroxylase encoded by CYP24A1] to neonatal 25(OH)D concentrations. Design: We used the classical twin study design to determine the genetic contribution to neonatal 25(OH)D. A total of 86 twin pairs (32 monozygotic and 54 dizygotic twin pairs) were included in this study. Serum 25(OH)D was measured by using a 25(OH)D kit. CYP24A1 promoter DNA methylation was measured by means of matrix-assisted laser desorption time-of-flight mass spectrometry. Results: Maternal and neonatal 25(OH)D showed a strong association (R = 0.19). Monozygotic and dizygotic within-pair serum 25(OH)D correlations were similar (R = 0.71 and 0.67, respectively), which suggested no genetic effect. Placental CYP24A1 methylation did not show an association with maternal or neonatal 25(OH)D

[1]  Christine L. Taylor,et al.  Dietary Reference Intakes for Calcium and Vitamin D , 2016, Pediatric Clinical Practice Guidelines & Policies.

[2]  Glenville Jones,et al.  25-Hydroxyvitamin D-24-hydroxylase (CYP24A1): its important role in the degradation of vitamin D. , 2012, Archives of biochemistry and biophysics.

[3]  Linhuan Huang,et al.  Selective and non-selective intrauterine growth restriction in twin pregnancies: high-risk factors and perinatal outcome , 2012, Archives of Gynecology and Obstetrics.

[4]  J. Carlin,et al.  COHORT PROFILE Cohort Profile : The Peri / post-natal Epigenetic Twins Study , 2012 .

[5]  Wendy P Robinson,et al.  Evidence for widespread changes in promoter methylation profile in human placenta in response to increasing gestational age and environmental/stochastic factors , 2011, BMC Genomics.

[6]  Scott M Langevin,et al.  In Utero Exposures, Infant Growth, and DNA Methylation of Repetitive Elements and Developmentally Related Genes in Human Placenta , 2011, Environmental health perspectives.

[7]  Grant W. Montgomery,et al.  Impact of the Genome on the Epigenome Is Manifested in DNA Methylation Patterns of Imprinted Regions in Monozygotic and Dizygotic Twins , 2011, PloS one.

[8]  M. Whiting,et al.  The correlation between third-trimester maternal and newborn-serum 25-hydroxy-vitamin D in a selected South Australian group of newborn samples , 2011, BMJ Open.

[9]  C. Morrison,et al.  Differential vitamin D 24-hydroxylase/CYP24A1 gene promoter methylation in endothelium from benign and malignant human prostate , 2011, Epigenetics.

[10]  Thomas J. Wang,et al.  Vitamin D and cardiovascular disease , 2011, Current opinion in nephrology and hypertension.

[11]  Devin C Koestler,et al.  Infant growth restriction is associated with distinct patterns of DNA methylation in human placentas , 2011, Epigenetics.

[12]  L. Lambertini,et al.  Differential Methylation of Imprinted Genes in Growth-Restricted Placentas , 2011, Reproductive Sciences.

[13]  C. Wagner,et al.  Maternal vitamin D and fetal growth in early-onset severe preeclampsia. , 2011, American journal of obstetrics and gynecology.

[14]  V. Lagishetty,et al.  Vitamin D and the Regulation of Placental Inflammation , 2011, The Journal of Immunology.

[15]  Dong Li,et al.  Detection of global DNA methylation and paternally imprinted H19 gene methylation in preeclamptic placentas , 2011, Hypertension Research.

[16]  C. Marsit,et al.  Birthweight is associated with DNA promoter methylation of the glucocorticoid receptor in human placenta , 2011, Epigenetics.

[17]  R. Weksberg,et al.  WNT2 promoter methylation in human placenta is associated with low birthweight percentile in the neonate , 2011, Epigenetics.

[18]  V. Vaccarino,et al.  Heritability and seasonal variability of vitamin D concentrations in male twins. , 2010, The American journal of clinical nutrition.

[19]  M. Longtine,et al.  Vitamin D effects on pregnancy and the placenta. , 2010, Placenta.

[20]  R. Saffery,et al.  DNA methylation profiling highlights the unique nature of the human placental epigenome. , 2010, Epigenomics.

[21]  John B Carlin,et al.  DNA methylation analysis of multiple tissues from newborn twins reveals both genetic and intrauterine components to variation in the human neonatal epigenome. , 2010, Human molecular genetics.

[22]  C. Wagner,et al.  Plasma 25-hydroxyvitamin D levels in early-onset severe preeclampsia. , 2010, American journal of obstetrics and gynecology.

[23]  C. Morrison,et al.  Epigenetic regulation of vitamin D 24-hydroxylase/CYP24A1 in human prostate cancer. , 2010, Cancer research.

[24]  R. Yuen,et al.  DNA methylation profiling of human placentas reveals promoter hypomethylation of multiple genes in early-onset preeclampsia , 2010, European Journal of Human Genetics.

[25]  William Wheeler,et al.  Genome-wide association study of circulating vitamin D levels , 2010, Human molecular genetics.

[26]  P. Papapetrou.  The interrelationship of serum 1,25-dihydroxyvitamin D, 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D in pregnancy at term: a meta-analysis , 2010, Hormones.

[27]  R. Saffery,et al.  A convergent model for placental dysfunction encompassing combined sub-optimal one-carbon donor and vitamin D bioavailability. , 2009, Medical hypotheses.

[28]  D. Eyles,et al.  Vitamin D, a neuro-immunomodulator: Implications for neurodegenerative and autoimmune diseases , 2009, Psychoneuroendocrinology.

[29]  A. Wolk,et al.  Seasonal Genetic Influence on Serum 25-Hydroxyvitamin D Levels: A Twin Study , 2009, PloS one.

[30]  C. Marsit,et al.  REVIEW ARTICLE: Epigenetics in the Placenta , 2009, American journal of reproductive immunology.

[31]  T. Down,et al.  Placenta-specific Methylation of the Vitamin D 24-Hydroxylase Gene , 2009, Journal of Biological Chemistry.

[32]  M. Pertile,et al.  Methylation of the adenomatous polyposis coli (APC) gene in human placenta and hypermethylation in choriocarcinoma cells. , 2008, Cancer letters.

[33]  T. Down,et al.  Specific tumour-associated methylation in normal human term placenta and first-trimester cytotrophoblasts. , 2008, Molecular human reproduction.

[34]  C. Kovacs.  Vitamin D in pregnancy and lactation: maternal, fetal, and neonatal outcomes from human and animal studies. , 2008, The American journal of clinical nutrition.

[35]  A. Morris,et al.  Evidence for genetic regulation of vitamin D status in twins with multiple sclerosis , 2008, The American journal of clinical nutrition.

[36]  Lisa M Bodnar,et al.  Maternal vitamin D deficiency increases the risk of preeclampsia. , 2007, The Journal of clinical endocrinology and metabolism.

[37]  M. Holick.  Vitamin D deficiency. , 2007, The New England journal of medicine.

[38]  John K Field,et al.  Quantitative high-throughput analysis of DNA methylation patterns by base-specific cleavage and mass spectrometry. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[39]  J. Kingdom,et al.  Discordant growth in twins , 2005, Prenatal diagnosis.

[40]  Glenville Jones,et al.  Enzymes involved in the activation and inactivation of vitamin D. , 2004, Trends in biochemical sciences.

[41]  G. Machin.  Why is it important to diagnose chorionicity and how do we do it? , 2004, Best practice & research. Clinical obstetrics & gynaecology.

[42]  L. Dodds,et al.  Does chorionicity or zygosity predict adverse perinatal outcomes in twins? , 2002, American journal of obstetrics and gynecology.

[43]  Albert B. Becker,et al.  Twin zygosity. Automated determination with microsatellites. , 1997, The Journal of reproductive medicine.

[44]  M. Ehrlich,et al.  The 5-methylcytosine content of highly repeated sequences in human DNA. , 1983, Nucleic acids research.

[45]  H. DeLuca,et al.  Maternal and fetal serum 1,25-dihydroxyvitamin D levels at term. , 1980, The Journal of pediatrics.

[46]  T. Günay,et al.  Vitamin D Requirements and Supplementation during Pregnancy , 2013 .

[47]  N. Binkley,et al.  The C-3 epimer of 25-hydroxyvitamin D(3) is present in adult serum. , 2012, The Journal of clinical endocrinology and metabolism.

[48]  J. Stockman.  Common genetic determinants of vitamin D insufficiency: a genome-wide association study , 2012 .