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

Background: Prenatal vitamin D ₃ 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 D ₃ 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 (COPSAC ₂₀₁₀ , 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 D ₃ supplementation versus placebo.
Results: Offspring of mothers with the low-risk GG or GC genotype who received high-dose vitamin D ₃ 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 COPSAC ₂₀₁₀ ), 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 COPSAC ₂₀₁₀ ).
Conclusion: Maternal 17q21 genotype has an important influence on the protective effects of prenatal vitamin D ₃ supplementation against offspring asthma/recurrent wheeze.
Competing Interests: Conflict of interest: H.M. Knihtilä has nothing to disclose. Conflict of interest: R.S. Kelly has nothing to disclose. Conflict of interest: N. Brustad has nothing to disclose. Conflict of interest: M. Huang has nothing to disclose. Conflict of interest: P. Kachroo has nothing to disclose. Conflict of interest: B.L. Chawes has nothing to disclose. Conflict of interest: J. Stokholm has nothing to disclose. Conflict of interest: K. Bønnelykke has nothing to disclose. Conflict of interest: C-E.T. Pedersen has nothing to disclose. Conflict of interest: H. Bisgaard has nothing to disclose. Conflict of interest: A.A. Litonjua reports author royalties from UpToDate, Inc., outside the submitted work. Conflict of interest: J.A. Lasky-Su has nothing to disclose. Conflict of interest: S.T. Weiss has nothing to disclose.
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