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 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.
Footnotes
This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.
Conflict of interest: Dr. Knihtilä has nothing to disclose.
Conflict of interest: Dr. Kelly has nothing to disclose.
Conflict of interest: Dr. Brustad has nothing to disclose.
Conflict of interest: Dr. Huang has nothing to disclose.
Conflict of interest: Dr. Kachroo has nothing to disclose.
Conflict of interest: Dr. Chawes has nothing to disclose.
Conflict of interest: Dr. Stokholm has nothing to disclose.
Conflict of interest: Dr. Bønnelykke has nothing to disclose.
Conflict of interest: Dr. Bisgaard has nothing to disclose.
Conflict of interest: Dr. Litonjua reports personal fees from UpToDate, Inc, outside the submitted work; .
Conflict of interest: Dr. Lasky-Su has nothing to disclose.
Conflict of interest: Dr. Weiss has nothing to disclose.
This is a PDF-only article. Please click on the PDF link above to read it.
- Received May 26, 2020.
- Accepted February 4, 2021.
- ©The authors 2021. For reproduction rights and permissions contact permissions{at}ersnet.org