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Title: Genetic link determining the maternal-fetal circulation of vitamin D
Authors: Sampathkumar, Aparna
Tan, Karen M.
Chen, Li
Chong, Mary F. F.
Yap, Fabian
Godfrey, Keith M.
Chong, Yap Seng
Gluckman, Peter D.
Ramasamy, Adaikalavan
Karnani, Neerja
Keywords: Science::Medicine
Issue Date: 2021
Source: Sampathkumar, A., Tan, K. M., Chen, L., Chong, M. F. F., Yap, F., Godfrey, K. M., Chong, Y. S., Gluckman, P. D., Ramasamy, A. & Karnani, N. (2021). Genetic link determining the maternal-fetal circulation of vitamin D. Frontiers in Genetics, 12, 721488-.
Project: NMRC/TCR/004-NUS/2008 
Journal: Frontiers in Genetics 
Abstract: Vitamin D is an essential micronutrient whose demand is heightened during pregnancy to support the growth of the fetus. Furthermore, the fetus does not produce vitamin D and hence relies exclusively on the supply of maternal vitamin D through the placenta. Vitamin D inadequacy is linked with pregnancy complications and adverse infant outcomes. Hence, early predictive markers of vitamin D inadequacy such as genetic vulnerability are important to both mother and offspring. In this multi-ethnic Asian birth cohort study, we report the first genome-wide association analysis (GWAS) of maternal and fetal vitamin D in circulation. For this, 25-hydroxyvitamin D (25OHD) was measured in the antenatal blood of mothers during mid gestation (n=942), and the cord blood of their offspring at birth (n=812). Around ~7 million single nucleotide polymorphisms (SNPs) were regressed against 25OHD concentrations to identify genetic risk variants. About 41% of mothers had inadequate 25OHD (≤75nmol/L) during pregnancy. Antenatal 25OHD was associated with ethnicity [Malay (Β=-22.32nmol/L, p=2.3×10-26); Indian (Β=-21.85, p=3.1×10-21); reference Chinese], age (Β=0.47/year, p=0.0058), and supplement intake (Β=16.47, p=2.4×10-13). Cord blood 25OHD highly correlated with antenatal vitamin D (r=0.75) and was associated with ethnicity [Malay (Β=-4.44, p=2.2×10-7); Indian (Β=-1.99, p=0.038); reference Chinese]. GWAS analysis identified rs4588, a missense variant in the group-specific component (GC) gene encoding vitamin D binding protein (VDBP), and its defining haplotype, as a risk factor for low antenatal (Β=-8.56/T-allele, p=1.0×10-9) and cord blood vitamin D (Β=-3.22/T-allele, p=1.0×10-8) in all three ethnicities. We also discovered a novel association in a SNP downstream of CYP2J2 (rs10789082), a gene involved in 25-hydroxylation of vitamin D, with vitamin D in pregnant women (Β=-7.68/G-allele, p=1.5×10-8), but not their offspring. As the prevention and early detection of suboptimal vitamin D levels are of profound importance to both mother and offspring's health, the genetic risk variants identified in this study allow risk assessment and precision in early intervention of vitamin D deficiency.
ISSN: 1664-8021
DOI: 10.3389/fgene.2021.721488
Schools: Lee Kong Chian School of Medicine (LKCMedicine) 
Organisations: Genome Institute of Singapore (GIS), A*STAR
Rights: Copyright © 2021 Sampathkumar, Tan, Chen, Chong, Yap, Godfrey, Chong, Gluckman, Ramasamy and Karnani. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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