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, theGT/TT genotype; high, the GG genotype)。

結果
1 歳時の低血清 25(OH)D3 level (≤50nM/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
10.8

10.64

0.60.40.200.1

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1412108642012.6

1

P=0.641.3

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

affectingvitaminD-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.
• Polymorphisms affecting vitamin D-binding
protein modify the relationship between 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• 1MurdochChildrens

ResearchInstitute,

Parkville, Australia; School of Population andGlobal

Health,UniversityofMelbourne,Parkville,Australia.2MurdochChildrens

ResearchInstitute,

Australia;

Parkville,

Department of Paediatrics, University ofMelbourne,Parkville,Childrens

ResearchAustralia;

ChildBarwon

HealthAustralia.3Murdoch
Institute,HealthandParkville,

ResearchUnit,

DeakinUniversity,Geelong,Australia.4MurdochChildrens

ResearchInstitute,Parkville,Australia.5European Centre for Environmentand Human Health, University of Exeter
MedicalSchool,Cornwall,UnitedKingdom.6MurdochChildrens

ResearchInstitute, Parkville, Australia; Department ofPaediatrics,

UniversityofMelbourne,Parkville, Australia; Department of Allergyand Immunology, Royal Children's Hospital,

Parkville,Australia.7MurdochChildrens

ResearchInstitute,Australia;

Parkville,Department of Paediatrics, University ofMelbourne, Parkville, Australia; Centre forCommunity Child Health, Royal Children'sHospital,Parkville,

Australia.8SchoolofPopulation and Global Health, University ofMelbourne,Parkville,Australia.9MurdochChildrensResearchAustralia;

Department

Institute,ofParkville,Paediatrics,

University of Melbourne, Parkville, Australia;
Department of Allergy and Immunology, RoyalChildren's

Hospital,

Parkville,

Australia;

School of Inflammation and Repair, Universityof Manchester, Manchester, United Kingdom.
Electronic address: katie.allen@rch.org.au.
• Abstract• BACKGROUND:• There is evolving evidence that vitamin D
insufficiency may contribute to food allergy,
but findings vary between populations. Lower
vitaminD-bindingprotein(DBP)levelsincrease the biological availability of serum
vitamin D. Genetic polymorphisms explain
almost 80% of the variation in binding protein
levels.
• OBJECTIVE:• Wesought

toinvestigate

whetherpolymorphisms 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 controlparticipants) and age 2 years (55 participants
with persistent and 50 participants withresolved food allergy). 25(OH)D3 levels weremeasured

usingliquid

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, theGT/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)
genotypes

butnot(OR,P interaction =inthosewithGT/TT0.7;

95%CI,0.2-2.0;.014).

Maternalantenatal

vitamin D supplementation was associatedwith 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 foodallergy(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

withgreater

vitaminD

bioavailability in those with a lower DBP level.
This increases the biological plausibility of arole for vitamin D in the development of foodallergy.