title: Polymorphisms affecting vitamin D-binding protein modify the relationship between serum vitamin D (25[OH]D3) and food allergy.
abstract: BACKGROUND
  There is evolving evidence that vitamin D insufficiency may contribute to food allergy, but findings vary between populations. Lower vitamin D-binding protein (DBP) levels increase the biological availability of serum vitamin D. Genetic polymorphisms explain almost 80% of the variation in binding protein levels.
  
  
  OBJECTIVE
  We sought to investigate whether polymorphisms that lower the DBP could compensate for adverse effects of low serum vitamin D on food allergy risk.
  
  
  METHODS
  From a population-based cohort study (n = 5276) we investigated the association between serum 25-hydroxyvitamin D3 (25[OH]D3) levels and food allergy at age 1 year (338 challenge-proven food-allergic and 269 control participants) and age 2 years (55 participants with persistent and 50 participants with resolved food allergy). 25(OH)D3 levels were measured using liquid chromatography-tandem mass spectrometry and adjusted for season of blood draw. Analyses were stratified by genotype at rs7041 as a proxy marker of DBP levels (low, the GT/TT genotype; high, the GG genotype).
  
  
  RESULTS
  Low serum 25(OH)D3 level (≤50 nM/L) at age 1 years was associated with food allergy, particularly among infants with the GG genotype (odds ratio [OR], 6.0; 95% CI, 0.9-38.9) but not in those with GT/TT genotypes (OR, 0.7; 95% CI, 0.2-2.0; P interaction = .014). Maternal antenatal vitamin D supplementation was associated with less food allergy, particularly in infants with the GT/TT genotype (OR, 0.10; 95% CI, 0.03-0.41). Persistent vitamin D insufficiency increased the likelihood of persistent food allergy (OR, 12.6; 95% CI, 1.5-106.6), particularly in those with the GG genotype.
  
  
  CONCLUSIONS
  Polymorphisms associated with lower DBP level attenuated the association between low serum 25(OH)D3 level and food allergy, consistent with greater vitamin D bioavailability in those with a lower DBP level. This increases the biological plausibility of a role for vitamin D in the development of food allergy.
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Australia; School of Population and Global Health, University of Melbourne, Parkville, Australia.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Koplin
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Australia; Department of Paediatrics, University of Melbourne, Parkville, Australia.
authors.forename: Noor H A
authors.initials: NH
authors.lastname: Suaini
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Australia; Child Health Research Unit, Barwon Health and Deakin University, Geelong, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Vuillermin
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Australia; Department of Paediatrics, University of Melbourne, Parkville, Australia.
authors.forename: Justine A
authors.initials: JA
authors.lastname: Ellis
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Australia.
authors.forename: Mary
authors.initials: M
authors.lastname: Panjari
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Australia; Department of Paediatrics, University of Melbourne, Parkville, Australia.
authors.forename: Anne-Louise
authors.initials: AL
authors.lastname: Ponsonby
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Australia; Department of Paediatrics, University of Melbourne, Parkville, Australia.
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Peters
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Australia; School of Population and Global Health, University of Melbourne, Parkville, Australia.
authors.forename: Melanie C
authors.initials: MC
authors.lastname: Matheson
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Australia; Department of Paediatrics, University of Melbourne, Parkville, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Martino
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Australia.
authors.forename: Thanh
authors.initials: T
authors.lastname: Dang
authors.affiliation: European Centre for Environment and Human Health, University of Exeter Medical School, Cornwall, United Kingdom.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Osborne
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Australia.
authors.forename: Pamela
authors.initials: P
authors.lastname: Martin
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Australia; School of Population and Global Health, University of Melbourne, Parkville, Australia.
authors.forename: Adrian
authors.initials: A
authors.lastname: Lowe
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Australia; School of Population and Global Health, University of Melbourne, Parkville, Australia.
authors.forename: Lyle C
authors.initials: LC
authors.lastname: Gurrin
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Australia; Department of Paediatrics, University of Melbourne, Parkville, Australia; Department of Allergy and Immunology, Royal Children's Hospital, Parkville, Australia.
authors.forename: Mimi L K
authors.initials: ML
authors.lastname: Tang
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Australia; Department of Paediatrics, University of Melbourne, Parkville, Australia; Centre for Community Child Health, Royal Children's Hospital, Parkville, Australia.
authors.forename: Melissa
authors.initials: M
authors.lastname: Wake
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Australia.
authors.forename: Terry
authors.initials: T
authors.lastname: Dwyer
authors.affiliation: School of Population and Global Health, University of Melbourne, Parkville, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Hopper
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Australia; School of Population and Global Health, University of Melbourne, Parkville, Australia.
authors.forename: Shyamali C
authors.initials: SC
authors.lastname: Dharmage
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Australia; Department of Paediatrics, University of Melbourne, Parkville, Australia; Department of Allergy and Immunology, Royal Children's Hospital, Parkville, Australia; School of Inflammation and Repair, University of Manchester, Manchester, United Kingdom. Electronic address: katie.allen@rch.org.au.
authors.forename: Katrina J
authors.initials: KJ
authors.lastname: Allen
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D002112:Calcifediol / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D019587:Dietary Supplements; D005260:Female; D005500:Follow-Up Studies; D005512:Food Hypersensitivity / Q000097:blood* / Q000453:epidemiology / Q000235:genetics*; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011159:Population Surveillance; D012306:Risk; D012621:Seasons; D014809:Vitamin D-Binding Protein / Q000235:genetics*; D055815:Young Adult
chemical_list: D014809:Vitamin D-Binding Protein; D002112:Calcifediol
keywords: Food hypersensitivity; food allergy; gene; polymorphism; vitamin D; vitamin D binding protein