A genetic approach to study the relationship between maternal Vitamin D status and newborn anthropometry measurements: the Vitamin D pregnant mother (VDPM) cohort study

Arif Sabta Aji,Julie Anne Lovegrove,Buthaina Alathari,Yusrawati Yusrawati,Safarina G Malik,Karani Santhanakrishnan Vimaleswaran,Rosfita Rasyid,Nur Indrawaty Lipoeto,Erwinda Erwinda

doi:10.1007/s40200-019-00480-5

Abstract

PurposeAdverse effects of maternal vitamin D deficiency have been linked to adverse pregnancy outcomes. We investigated the relationship between maternal vitamin D status and newborn anthropometry measurements using a genetic approach and examined the interaction between genetic variations in involved in vitamin D synthesis and metabolism and maternal vitamin D concentrations on newborn anthropometry.MethodsThe study was conducted in 183 pregnant Indonesian Minangkabau women. Genetic risk scores (GRSs) were created using six vitamin D–related single nucleotide polymorphisms and their association with 25-hydroxyvitamin D [25(OH)D] levels and newborn anthropometry (183 infants) were investigated.ResultsThere was no significant association between maternal 25(OH)D concentrations and newborn anthropometry measurements (P > 0.05, for all comparisons). After correction for multiple testing using Bonferroni correction, GRS was significantly associated with 25(OH)D in the third trimester (P = 0.004). There was no association between GRS and newborn anthropometric measurements; however, there was an interaction between GRS and 25(OH)D on head circumference (P = 0.030), where mothers of neonates with head circumference < 35 cm had significantly lower 25(OH)D if they carried ≥4 risk alleles compared to those who carried ≤3 risk alleles.ConclusionOur findings demonstrate the impact of vitamin D-related GRS on 25(OH)D and provides evidence for the effect of vitamin D-related GRS on newborn anthropometry through the influence of serum 25(OH)D levels among Indonesian pregnant women. Even though our study is a prospective cohort, before the implementation of vitamin D supplementation programs in Indonesia to prevent adverse pregnancy outcomes, further large studies are required to confirm our findings.

Highlights

As one of the tropical countries in Southeast Asia located at the equator, Indonesia has an abundant sunlight all year round
Candidate gene studies have identified twelve genes based on the genome-wide association studies (GWAS) for 25(OH)D (GC, CYP24A1, CYP2R1, DHCR7) [12], GWAS for skin colour/tanning (interferon regulatory factor 4 (IRF4); melanocortin 1 receptor (MC1R); oculocutaneous albinism type 2 (OCA2); solute carrier family 45, member 2 (SLC45A2); tyrosinase (TYR)) [13,14,15], and candidate gene studies for vitamin D pathway genes (VDR, cytochrome P450, family 27, subfamily A, polypeptide 1 (CYP27A1); cytochrome P450, family 27, subfamily B, polypeptide 1 (CYP27B1)) [16]
Recent GWASs have confirmed the association of six genetic variants in the following genes (short/branched chain acyl-CoA dehydrogenase (ACADSB), GC, DHCR7, CYP2R1, and CYP24A1) with 25OHD levels [12, 17], and these variants were found near genes involved in cholesterol synthesis, hydroxylation, and vitamin D transport that affects vitamin D status

Summary

Introduction

As one of the tropical countries in Southeast Asia located at the equator, Indonesia has an abundant sunlight all year round. Candidate gene studies have identified twelve genes based on the genome-wide association studies (GWAS) for 25(OH)D (GC, CYP24A1, CYP2R1, DHCR7) [12], GWAS for skin colour/tanning (interferon regulatory factor 4 (IRF4); melanocortin 1 receptor (MC1R); oculocutaneous albinism type 2 (OCA2); solute carrier family 45, member 2 (SLC45A2); tyrosinase (oculocutaneous) (TYR)) [13,14,15], and candidate gene studies for vitamin D pathway genes (VDR, cytochrome P450, family 27, subfamily A, polypeptide 1 (CYP27A1); cytochrome P450, family 27, subfamily B, polypeptide 1 (CYP27B1)) [16]. Recent GWASs have confirmed the association of six genetic variants in the following genes (short/branched chain acyl-CoA dehydrogenase (ACADSB), GC, DHCR7, CYP2R1, and CYP24A1) with 25OHD levels [12, 17], and these variants were found near genes involved in cholesterol synthesis, hydroxylation, and vitamin D transport that affects vitamin D status. The metabolic pathways and synthesis of vitamin D are regulated by the specific genes present in the pathway and the pathway is initiated by the exposure to UVB rays (vitamin D3) and dietary intake of vitamin D sources (vitamin D2)

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