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

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 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.

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 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).

Conclusion Maternal 17q21 genotype has an important influence on the protective effects of prenatal vitamin D₃ supplementation against offspring asthma/recurrent wheeze.