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

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56 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)500-506.e4
JournalJournal of Allergy and Clinical Immunology
Issue number2
Publication statusPublished - 1 Feb 2016
Externally publishedYes


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