Polymorphisms affecting vitamin D-binding protein modify the relationship between serum vitamin D (25[OH]D3) and food allergy

Jennifer J Koplin; Noor H A Suaini; Peter Vuillermin; Justine A Ellis; Mary Panjari; Anne-Louise Ponsonby; Rachel L Peters; Melanie C Matheson; David Martino; Thanh Dang; Nicholas J Osborne; Pamela Martin; Adrian Lowe; Lyle C Gurrin; Mimi L K Tang; Melissa Wake; Terry Dwyer; John Hopper; Shyamali C Dharmage; Katrina J Allen; HealthNuts Study

doi:10.1016/j.jaci.2015.05.051

Polymorphisms affecting vitamin D-binding protein modify the relationship between serum vitamin D (25[OH]D3) and food allergy

J Allergy Clin Immunol. 2016 Feb;137(2):500-506.e4. doi: 10.1016/j.jaci.2015.05.051. Epub 2015 Aug 7.

Authors

Jennifer J Koplin¹, Noor H A Suaini², Peter Vuillermin³, Justine A Ellis², Mary Panjari⁴, Anne-Louise Ponsonby², Rachel L Peters², Melanie C Matheson¹, David Martino², Thanh Dang⁴, Nicholas J Osborne⁵, Pamela Martin⁴, Adrian Lowe¹, Lyle C Gurrin¹, Mimi L K Tang⁶, Melissa Wake⁷, Terry Dwyer⁴, John Hopper⁸, Shyamali C Dharmage¹, Katrina J Allen⁹; HealthNuts Study

Affiliations

¹ Murdoch Childrens Research Institute, Parkville, Australia; School of Population and Global Health, University of Melbourne, Parkville, Australia.
² Murdoch Childrens Research Institute, Parkville, Australia; Department of Paediatrics, University of Melbourne, Parkville, Australia.
³ Murdoch Childrens Research Institute, Parkville, Australia; Child Health Research Unit, Barwon Health and Deakin University, Geelong, Australia.
⁴ Murdoch Childrens Research Institute, Parkville, Australia.
⁵ European Centre for Environment and Human Health, University of Exeter Medical School, Cornwall, United Kingdom.
⁶ 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.
⁷ 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.
⁸ School of Population and Global Health, University of Melbourne, Parkville, Australia.
⁹ 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: [email protected].

PMID: 26260969
DOI: 10.1016/j.jaci.2015.05.051

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.

Keywords: Food hypersensitivity; food allergy; gene; polymorphism; vitamin D; vitamin D binding protein.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Alleles
Calcifediol / blood*
Child
Child, Preschool
Cohort Studies
Dietary Supplements
Female
Follow-Up Studies
Food Hypersensitivity / blood*
Food Hypersensitivity / epidemiology
Food Hypersensitivity / genetics*
Genetic Association Studies*
Genotype
Humans
Infant
Male
Odds Ratio
Polymorphism, Single Nucleotide*
Population Surveillance
Risk
Seasons
Vitamin D-Binding Protein / genetics*
Young Adult

Substances

Vitamin D-Binding Protein
Calcifediol