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.

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 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).

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

产前补充维生素 D ₃与降低早期哮喘/复发性喘息的风险有关。这种保护作用似乎受到儿童 17q21 功能性单核苷酸多态性 rs12936231 变异的影响，该多态性调节ORMDL3（ORM1 样 3）的表达，并且高风险 CC 基因型与早发性哮喘相关。然而，这并不能完全解释补充剂的差异效应。_{我们研究了母亲 rs12936231 基因型变异对产前补充维生素 D 3}对后代哮喘/复发性喘息的保护作用的影响。

我们通过两项随机对照试验确定了母子对的 rs12936231 基因型：维生素 D 产前哮喘减少试验 (VDAART，n=613) 和 2010 年哥本哈根儿童哮喘前瞻性研究 (COPSAC 2010，_n =563)，以检查接受高剂量产前维生素 D ₃补充剂与安慰剂组之间母亲基因型变异对 0-3 岁时哮喘/复发性喘息的影响。

与安慰剂组相比，接受高剂量维生素 D ₃补充剂的低风险 GG 或 GC 基因型母亲的后代患哮喘/复发性喘息的风险显着降低（风险比 (HR) 0.54，95% CI 0.37– 0.77；对于 VDAART 和 HR 0.56，p<0.001，95% CI 0.35-0.92；对于 COPSAC ₂₀₁₀ ，p=0.021 ），而在具有高风险 CC 基因型的母亲的后代中没有观察到差异（HR 1.05，95% CI） 0.61–1.84；VDAART 的 p=0.853，HR 1.11，95% CI 0.54–2.28；COPSAC ₂₀₁₀的 p=0.785 ）。

_{母体 17q21 基因型对产前补充维生素 D 3}对后代哮喘/复发性喘息的保护作用具有重要影响。