ビタミンＤ結合タンパクに影響する遺伝子多型が血清ビタミンＤ(25[OH]D3)と食物アレルギーとの関係を修正する

背景
ビタミンＤ不足が食物アレルギーと関連しているというエビデンスが増加している。
ビタミンＤ結合タンパク（DBD)低下が血清ビタミン D 生物学的活性を増加させる。遺伝的多型が結合タンパクの変化の 80％を説明出来る。
目的
DBP の低下が食物アレルギーにおける血清ビタミン D 低下による悪影響を代償することが出来るかについて調べた。
方法
集団ベース研究(n=5276)より血清 serum 25-hydroxyvitamin D3 (25[OH]D3) と 1歳時の食物アレルギー（負荷試験で証明した 338 名の食物アレルギーと 269 名のコントロール）と 2 歳時（55 名の持続した食物アレルギーと寛解した 50 名）との関連について調べた。液体クロマトグラフィータンデムマススペクトロメトリーにて 25(OH)D3 値を測定し、季節で補正した。解析は DBP 代理のマーカとして rs7041 のゲノム型によって層別化した (low, the GT/TT genotype; high, the GG genotype)。
結果
1 歳時の低血清 25(OH)D3 level (≤50 nM/L) 値は食物アレルギーと関連した。
特に GG ゲノム型の乳児で(オッズ比 [OR], 6.0; 95% CI, 0.9-38.9) 、しかし GT/TT ゲノム型では関連しなかった (OR, 0.7; 95% CI, 0.2-2.0; P interaction = .014)。母親の出生前のビタミンＤサプリメントは食物アレルギーの減少と関連した、特に GT/TT ゲノム型 (OR,0.10; 95% CI, 0.03-0.41)。
持続的なビタミン D 不足は持続的食物アレルギーを増加させ(OR,12.6; 95% CI, 1.5-106.6)、特に GG ゲノム型においてみられた。
結論
DBP 値の低下と関連した遺伝的多型は低血清 25(OH)D3 と食物アレルギーとの関連を弱めた。そのことは低 DBP を伴ったビタミンＤ生物学的活性が高くなることと一致する。これは食物アレルギーにおけるビタミンＤの役割をうまく説明できる。

妊娠中の総合ビタミン剤・ビタミンＤと１歳時の食物アレルギーオッズ比Koplin JJ Polymorphisms affecting Vitamin D-binding protein modify the relationship between serum Vitamin D (25[OH]D3) and food allergy JACI 2016 137 500-6.

オッズ比
1.2

110.64

0.8
0.6
0.4

0.1

0.2
0

1歳時・2歳時のビタミンＤと2歳時の鶏卵アレルギーオッズ比Koplin JJ Polymorphisms affecting Vitamin D-binding protein modify the relationship between serum Vitamin D (25[OH]D3) and food allergy JACI 2016 137 500-6.

P=0.020

オッズ比1412108642012.61P=0.64
1.3

P=0.280.7

食物アレルギーのある人はビタミンＤのサプリメントとしての摂取が、食物アレルギーを改善する可能性がある

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

ClinImmunol.

2016

Feb;137(2):500-506.e4.

doi:10.1016/j.jaci.2015.05.051. Epub 2015 Aug 7.
•

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

•Koplin JJ1, Suaini NH2, Vuillermin P3, Ellis JA2, Panjari M4, Ponsonby AL2,Peters RL2, Matheson MC1, Martino D2, Dang T4, Osborne NJ5, Martin P4, Lowe
A1, Gurrin LC1, Tang ML6, Wake M7, Dwyer T4, Hopper J8, Dharmage SC1, Allen
KJ9; HealthNuts Study.

•Author information•1Murdoch Childrens Research Institute, Parkville, Australia; School of
Population

andGlobal

Australia.2Murdoch
DepartmentofHealth,Childrens

University

Research

Paediatrics,ofMelbourne,Parkville,Parkville,Australia;

Melbourne,Parkville,Institute,University

ofAustralia.3Murdoch Childrens Research Institute, Parkville, Australia; ChildHealth Research Unit, Barwon Health and Deakin University, Geelong,
Australia.4MurdochChildrensResearchInstitute,Parkville,Australia.5European Centre for Environment and Human Health, University of
Exeter Medical School, Cornwall, United Kingdom.6Murdoch Childrens
Research Institute, Parkville, Australia; Department of Paediatrics, Universityof Melbourne, Parkville, Australia; Department of Allergy and Immunology,
Royal Children's Hospital, Parkville, Australia.7Murdoch Childrens ResearchInstitute, Parkville, Australia; Department of Paediatrics, University ofMelbourne, Parkville, Australia; Centre for Community Child Health, RoyalChildren's Hospital, Parkville, Australia.8School of Population and Global
Health, University of Melbourne, Parkville, Australia.9Murdoch Childrens
Research Institute, Parkville, Australia; Department of Paediatrics, Universityof Melbourne, Parkville, Australia; Department of Allergy and Immunology,
Royal Children's Hospital, Parkville, Australia; School of Inflammation andRepair, University of Manchester, Manchester, United Kingdom. Electronic
address: katie.allen@rch.org.au.
•Abstract•

BACKGROUND:•There is evolving evidence that vitamin D insufficiency may contribute to foodallergy, 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 foodallergy). 25(OH)D3 levels were measured using liquid chromatography-tandem
mass spectrometry and adjusted for season of blood draw. Analyses werestratified by genotype at rs7041 as a proxy marker of DBP levels (low, the GT/TTgenotype; high, the GG genotype).

•RESULTS:•Low serum 25(OH)D3 level (≤50 nM/L) at age 1 years was associated with foodallergy, 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/TTgenotype (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.