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 SNP rs12936231 of the child, which regulates the expression of ORMDL3, 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.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.Offspring of mothers with low-risk GG-genotype or GC-genotype who received high-dose vitamin D3 supplementation had a significantly reduced risk of asthma/recurrent wheeze when compared to the placebo group (hazard ratio [HR], 0.54; 95% confidence interval [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 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).Maternal 17q21 genotype has an important influence on the protective effects of prenatal vitamin D3 supplementation against offspring asthma/recurrent wheeze.
Hanna M Knihtilä, Rachel S Kelly, Nicklas Brustad, Mengna Huang, Priyadarshini Kachroo, Bo L Chawes, Jakob Stokholm, Klaus Bønnelykke, Casper-Emil T Pedersen, Hans Bisgaard, Augusto A Litonjua, Jessica A Lasky-Su, Scott T Weiss