Maternal vitamin D predominates over genetic factors in determining neonatal circulating vitamin D concentrations.
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.


METHODS
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 (R² = 0.19). Monozygotic and dizygotic within-pair serum 25(OH)D correlations were similar (R² = 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 concentrations.


CONCLUSIONS
Our results suggest that maternal circulating 25(OH)D is the most significant regulator of neonatal circulating 25(OH)D concentrations, with underlying genetic factors playing a limited role. The placental methylation of the CYP24A1 promoter appears subject to a genetic influence, although no evidence of a relation between the methylation level of this gene and circulating maternal or neonatal 25(OH)D was apparent.
Cancer and Disease Epigenetics Group, Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, Australia.
Boris
B
Novakovic
John C
JC
Galati
Anna
A
Chen
Ruth
R
Morley
Jeffrey M
JM
Craig
Richard
R
Saffery
D015652:25-Hydroxyvitamin D 2 / Q000097:blood; D002112:Calcifediol / Q000097:blood*; D019175:DNA Methylation; D005260:Female; D005312:Fetal Blood; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood* / Q000235:genetics; D011401:Promoter Regions, Genetic; D013250:Steroid Hydroxylases / Q000235:genetics* / Q000378:metabolism; D014429:Twins, Dizygotic; D014430:Twins, Monozygotic; D014739:Victoria; D014808:Vitamin D Deficiency / Q000097:blood* / Q000151:congenital / Q000235:genetics; D065668:Vitamin D3 24-Hydroxylase
D015652:25-Hydroxyvitamin D 2; D013250:Steroid Hydroxylases; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase; D002112:Calcifediol