Environmental and genetic determinants of vitamin D insufficiency in 12-month-old infants

Suaini NH 1 , Koplin JJ 2 , Ellis JA 3 , Peters RL 3 , Ponsonby AL 3 , Dharmage SC 2 Show all authors , Matheson MC 4 , Wake M 5 , Panjari M 1 , Tan HT 6 , Martin PE 1 , Pezic A 1 , Lowe AJ 2 , Martino D 3 , Gurrin LC 2 , Vuillermin PJ 7 , Tang ML 8 , Allen KJ 9 , HealthNuts Study Investigators

Affiliations 

  • 1 Murdoch Childrens Research Institute, Parkville, Victoria 3052, Australia
  • 2 Murdoch Childrens Research Institute, Parkville, Victoria 3052, Australia; Centre for Epidemiology and Biostatistics, The University of Melbourne, Melbourne, Victoria, Australia
  • 3 Murdoch Childrens Research Institute, Parkville, Victoria 3052, Australia; Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia
  • 4 Centre for Epidemiology and Biostatistics, The University of Melbourne, Melbourne, Victoria, Australia
  • 5 Murdoch Childrens Research Institute, Parkville, Victoria 3052, Australia; Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia; Centre for Community Child Health, The Royal Children's Hospital, Melbourne, Victoria, Australia
  • 6 Murdoch Childrens Research Institute, Parkville, Victoria 3052, Australia; Department of Immunology, School of Medical Sciences, Universiti Sains Malaysia, Malaysia
  • 7 Murdoch Childrens Research Institute, Parkville, Victoria 3052, Australia; Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia; Deakin University, Geelong, Victoria, Australia; Child Health Research Unit, Barwon Health, Geelong, Victoria, Australia
  • 8 Murdoch Childrens Research Institute, Parkville, Victoria 3052, Australia; Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia; Department of Allergy and Immunology, The Royal Children's Hospital, Parkville, Victoria, Australia
  • 9 Murdoch Childrens Research Institute, Parkville, Victoria 3052, Australia; Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia; Department of Allergy and Immunology, The Royal Children's Hospital, Parkville, Victoria, Australia; School of Inflammation and Repair, University of Manchester, Manchester, UK. Electronic address: katie.allen@rch.org.au
J Steroid Biochem Mol Biol, 2014 Oct;144 Pt B:445-54.
PMID: 25174667 DOI: 10.1016/j.jsbmb.2014.08.018

Abstract

We aimed to investigate the relationship between genetic and environmental exposure and vitamin D status at age one, stratified by ethnicity. This study included 563 12-month-old infants in the HealthNuts population-based study. DNA from participants' blood samples was genotyped using Sequenom MassARRAY MALDI-TOF system on 28 single nucleotide polymorphisms (SNPs) in six genes. Using logistic regression, we examined associations between environmental exposure and SNPs in vitamin D pathway and filaggrin genes and vitamin D insufficiency (VDI). VDI, defined as serum 25-hydroxyvitamin D3(25(OH)D3) level ≤50nmol/L, was measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Infants were stratified by ethnicity determined by parent's country of birth. Infants formula fed at 12 months were associated with reduced odds of VDI compared to infants with no current formula use at 12 months. This association differed by ethnicity (Pinteraction=0.01). The odds ratio (OR) of VDI was 0.29 for Caucasian infants (95% CI, 0.18-0.47) and 0.04 for Asian infants (95% CI, 0.006-0.23). Maternal vitamin D supplementation during pregnancy and/or breastfeeding were associated with increased odds of infants being VDI (OR, 2.39; 95% CI, 1.11-5.18 and OR, 2.5; 95% CI, 1.20-5.24 respectively). Presence of a minor allele for any GC SNP (rs17467825, rs1155563, rs2282679, rs3755967, rs4588, rs7041) was associated with increased odds of VDI. Caucasian infants homozygous (AA) for rs4588 had an OR of 2.49 of being associated with VDI (95% CI, 1.19-5.18). In a country without routine infant vitamin D supplementation or food chain fortification, formula use is strongly associated with a reduced risk of VDI regardless of ethnicity. There was borderline significance for an association between filaggrin mutations and VDI. However, polymorphisms in vitamin D pathway related genes were associated with increased likelihood of being VDI in infancy.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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