title: Environmental and genetic determinants of vitamin D insufficiency in 12-month-old infants.
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.
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Victoria 3052, Australia.
authors.forename: Noor H A
authors.initials: NH
authors.lastname: Suaini
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Victoria 3052, Australia; Centre for Epidemiology and Biostatistics, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Koplin
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Victoria 3052, Australia; Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Justine A
authors.initials: JA
authors.lastname: Ellis
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Victoria 3052, Australia; Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Peters
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Victoria 3052, Australia; Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Anne-Louise
authors.initials: AL
authors.lastname: Ponsonby
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Victoria 3052, Australia; Centre for Epidemiology and Biostatistics, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Shyamali C
authors.initials: SC
authors.lastname: Dharmage
authors.affiliation: Centre for Epidemiology and Biostatistics, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Melanie C
authors.initials: MC
authors.lastname: Matheson
authors.affiliation: 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.
authors.forename: Melissa
authors.initials: M
authors.lastname: Wake
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Victoria 3052, Australia.
authors.forename: Mary
authors.initials: M
authors.lastname: Panjari
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Victoria 3052, Australia; Department of Immunology, School of Medical Sciences, Universiti Sains Malaysia, Malaysia.
authors.forename: Hern-Tze Tina
authors.initials: HT
authors.lastname: Tan
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Victoria 3052, Australia.
authors.forename: Pamela E
authors.initials: PE
authors.lastname: Martin
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Victoria 3052, Australia.
authors.forename: Angela
authors.initials: A
authors.lastname: Pezic
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Victoria 3052, Australia; Centre for Epidemiology and Biostatistics, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Lowe
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Victoria 3052, Australia; Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Martino
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Victoria 3052, Australia; Centre for Epidemiology and Biostatistics, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Lyle C
authors.initials: LC
authors.lastname: Gurrin
authors.affiliation: 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.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Vuillermin
authors.affiliation: 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.
authors.forename: Mimi L K
authors.initials: ML
authors.lastname: Tang
authors.affiliation: 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.
authors.forename: Katrina J
authors.initials: KJ
authors.lastname: Allen
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics; D044466:Asian People / Q000235:genetics; D001942:Breast Feeding; D053493:Cholestanetriol 26-Monooxygenase / Q000235:genetics; D000072467:Cytochrome P450 Family 2; D004032:Diet; D019587:Dietary Supplements; D004777:Environment; D004781:Environmental Exposure; D005260:Female; D000091344:Filaggrin Proteins; D006801:Humans; D007223:Infant; D041943:Infant Formula; D007381:Intermediate Filament Proteins / Q000235:genetics; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D018167:Receptors, Calcitriol / Q000235:genetics; D012621:Seasons; D014466:Ultraviolet Rays; D014739:Victoria / Q000453:epidemiology; D014807:Vitamin D / Q000008:administration & dosage; D014808:Vitamin D Deficiency / Q000453:epidemiology* / Q000209:etiology*; D014809:Vitamin D-Binding Protein / Q000235:genetics; D065668:Vitamin D3 24-Hydroxylase / Q000235:genetics; D044465:White People / Q000235:genetics
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D018167:Receptors, Calcitriol; D014809:Vitamin D-Binding Protein; D014807:Vitamin D; D000072467:Cytochrome P450 Family 2; C506833:CYP2R1 protein, human; D053493:Cholestanetriol 26-Monooxygenase; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase
keywords: Breastfeeding; Cohort studies; Genetic association studies; Infant formula; SNPs; Vitamin D