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Maternal 17q21 genotype influences prenatal vitamin D effects on offspring asthma/recurrent wheeze

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Knihtilä, Hanna M ; Kelly, Rachel S ; Brustad, Nicklas ; Huang, Mengna ; Kachroo, Priyadarshini ; Chawes, Bo L ; Stokholm, Jakob ; Bønnelykke, Klaus ; Pedersen, Casper-Emil T ; Bisgaard, Hans ; Litonjua, Augusto A ; Lasky-Su, Jessica A ; Weiss, Scott T. / Maternal 17q21 genotype influences prenatal vitamin D effects on offspring asthma/recurrent wheeze. I: The European respiratory journal. 2021 ; Bind 58, Nr. 3. s. 2002012.

Bibtex

@article{bbb0cff7a04044b89b8b92b637c4d43d,
title = "Maternal 17q21 genotype influences prenatal vitamin D effects on offspring asthma/recurrent wheeze",
abstract = "BACKGROUND: Prenatal vitamin D3 supplementation has been linked to reduced risk of early-life asthma/recurrent wheeze. This protective effect appears to be influenced by variations in the 17q21 functional single nucleotide polymorphism rs12936231 of the child, which regulates the expression of ORMDL3 (ORM1-like 3) and for which the high-risk CC genotype is associated with early-onset asthma. However, this does not fully explain the differential effects of supplementation. We investigated the influence of maternal rs12936231 genotype variation on the protective effect of prenatal vitamin D3 supplementation against offspring asthma/recurrent wheeze.METHODS: We determined the rs12936231 genotype of mother-child pairs from two randomised controlled trials: the Vitamin D Antenatal Asthma Reduction Trial (VDAART, n=613) and the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC2010, n=563), to examine the effect of maternal genotype variation on offspring asthma/recurrent wheeze at age 0-3 years between groups who received high-dose prenatal vitamin D3 supplementation versus placebo.RESULTS: Offspring of mothers with the low-risk GG or GC genotype who received high-dose vitamin D3 supplementation had a significantly reduced risk of asthma/recurrent wheeze when compared with the placebo group (hazard ratio (HR) 0.54, 95% CI 0.37-0.77; p<0.001 for VDAART and HR 0.56, 95% CI 0.35-0.92; p=0.021 for COPSAC2010), whereas no difference was observed among the offspring of mothers with the high-risk CC genotype (HR 1.05, 95% CI 0.61-1.84; p=0.853 for VDAART and HR 1.11, 95% CI 0.54-2.28; p=0.785 for COPSAC2010).CONCLUSION: Maternal 17q21 genotype has an important influence on the protective effects of prenatal vitamin D3 supplementation against offspring asthma/recurrent wheeze.",
author = "Knihtil{\"a}, {Hanna M} and Kelly, {Rachel S} and Nicklas Brustad and Mengna Huang and Priyadarshini Kachroo and Chawes, {Bo L} and Jakob Stokholm and Klaus B{\o}nnelykke and Pedersen, {Casper-Emil T} and Hans Bisgaard and Litonjua, {Augusto A} and Lasky-Su, {Jessica A} and Weiss, {Scott T}",
note = "{\textcopyright}The authors 2021. For reproduction rights and permissions contact permissions@ersnet.org.",
year = "2021",
month = sep,
doi = "10.1183/13993003.02012-2020",
language = "English",
volume = "58",
pages = "2002012",
journal = "European Respiratory Journal",
issn = "0903-1936",
publisher = "European Respiratory Society",
number = "3",

}

RIS

TY - JOUR

T1 - Maternal 17q21 genotype influences prenatal vitamin D effects on offspring asthma/recurrent wheeze

AU - Knihtilä, Hanna M

AU - Kelly, Rachel S

AU - Brustad, Nicklas

AU - Huang, Mengna

AU - Kachroo, Priyadarshini

AU - Chawes, Bo L

AU - Stokholm, Jakob

AU - Bønnelykke, Klaus

AU - Pedersen, Casper-Emil T

AU - Bisgaard, Hans

AU - Litonjua, Augusto A

AU - Lasky-Su, Jessica A

AU - Weiss, Scott T

N1 - ©The authors 2021. For reproduction rights and permissions contact permissions@ersnet.org.

PY - 2021/9

Y1 - 2021/9

N2 - BACKGROUND: Prenatal vitamin D3 supplementation has been linked to reduced risk of early-life asthma/recurrent wheeze. This protective effect appears to be influenced by variations in the 17q21 functional single nucleotide polymorphism rs12936231 of the child, which regulates the expression of ORMDL3 (ORM1-like 3) and for which the high-risk CC genotype is associated with early-onset asthma. However, this does not fully explain the differential effects of supplementation. We investigated the influence of maternal rs12936231 genotype variation on the protective effect of prenatal vitamin D3 supplementation against offspring asthma/recurrent wheeze.METHODS: We determined the rs12936231 genotype of mother-child pairs from two randomised controlled trials: the Vitamin D Antenatal Asthma Reduction Trial (VDAART, n=613) and the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC2010, n=563), to examine the effect of maternal genotype variation on offspring asthma/recurrent wheeze at age 0-3 years between groups who received high-dose prenatal vitamin D3 supplementation versus placebo.RESULTS: Offspring of mothers with the low-risk GG or GC genotype who received high-dose vitamin D3 supplementation had a significantly reduced risk of asthma/recurrent wheeze when compared with the placebo group (hazard ratio (HR) 0.54, 95% CI 0.37-0.77; p<0.001 for VDAART and HR 0.56, 95% CI 0.35-0.92; p=0.021 for COPSAC2010), whereas no difference was observed among the offspring of mothers with the high-risk CC genotype (HR 1.05, 95% CI 0.61-1.84; p=0.853 for VDAART and HR 1.11, 95% CI 0.54-2.28; p=0.785 for COPSAC2010).CONCLUSION: Maternal 17q21 genotype has an important influence on the protective effects of prenatal vitamin D3 supplementation against offspring asthma/recurrent wheeze.

AB - BACKGROUND: Prenatal vitamin D3 supplementation has been linked to reduced risk of early-life asthma/recurrent wheeze. This protective effect appears to be influenced by variations in the 17q21 functional single nucleotide polymorphism rs12936231 of the child, which regulates the expression of ORMDL3 (ORM1-like 3) and for which the high-risk CC genotype is associated with early-onset asthma. However, this does not fully explain the differential effects of supplementation. We investigated the influence of maternal rs12936231 genotype variation on the protective effect of prenatal vitamin D3 supplementation against offspring asthma/recurrent wheeze.METHODS: We determined the rs12936231 genotype of mother-child pairs from two randomised controlled trials: the Vitamin D Antenatal Asthma Reduction Trial (VDAART, n=613) and the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC2010, n=563), to examine the effect of maternal genotype variation on offspring asthma/recurrent wheeze at age 0-3 years between groups who received high-dose prenatal vitamin D3 supplementation versus placebo.RESULTS: Offspring of mothers with the low-risk GG or GC genotype who received high-dose vitamin D3 supplementation had a significantly reduced risk of asthma/recurrent wheeze when compared with the placebo group (hazard ratio (HR) 0.54, 95% CI 0.37-0.77; p<0.001 for VDAART and HR 0.56, 95% CI 0.35-0.92; p=0.021 for COPSAC2010), whereas no difference was observed among the offspring of mothers with the high-risk CC genotype (HR 1.05, 95% CI 0.61-1.84; p=0.853 for VDAART and HR 1.11, 95% CI 0.54-2.28; p=0.785 for COPSAC2010).CONCLUSION: Maternal 17q21 genotype has an important influence on the protective effects of prenatal vitamin D3 supplementation against offspring asthma/recurrent wheeze.

UR - http://www.scopus.com/inward/record.url?scp=85116767046&partnerID=8YFLogxK

U2 - 10.1183/13993003.02012-2020

DO - 10.1183/13993003.02012-2020

M3 - Journal article

C2 - 33653805

VL - 58

SP - 2002012

JO - European Respiratory Journal

JF - European Respiratory Journal

SN - 0903-1936

IS - 3

M1 - 2002012

ER -

ID: 64084085