Single nucleotide polymorphisms (SNPs) of the vitamin D receptor (VDR) gene have shown linkage and association with asthma development in multiple cohort studies. However, the majority of investigations have focused on asthma phenotypes in cohorts with stable disease. We investigated the relationship between VDR SNPs and the frequency and severity of acute episodes of wheeze/asthma in a cohort of Australian children, as the ability to identify children at risk of more severe exacerbations could lead to personalized and improved genotype-specific treatment pathways. We successfully genotyped five SNPs of the VDR gene (rs2525046, rs9729, rs1544410 (BsmI), rs22239179, and rs2228570 (FokI)) in 657 children presenting to a tertiary children's hospital with acute asthma, bronchiolitis, or a wheezing illness. The relationships between VDR SNPs and exacerbation severity scores, β2-agonist use, and frequency of respiratory exacerbations were analysed using multiple regression. The rs2525046 (FokI) CT genotype was associated with higher VDR mRNA intensity levels (p = 0.007) compared to the CC genotype. A trend towards significance (p=0.056) was identified between the rs2525046 TT genotype and higher VDR mRNA intensity levels compared to the CC genotype. Children with rs2228570 AA genotype had higher exacerbation severity scores (p=0.001) and poorer β2-agonist treatment response (doses at 6 h: p = 0.009 and 12 h: p=0.033) compared to those with the GG genotype. Children with rs1544410 (BsmI) TT genotype had lower exacerbation severity scores (p = 0.005) compared to those with the CC genotype. Children with rs2228570 GA genotype presented to and/or were admitted to hospital more times since birth with respiratory (p = 0.011) and wheezing (p = 0.021) illnesses than children with the GG genotype. No associations were identified between rs9729, rs2525046 and r2239179 polymorphisms and acute wheezing/asthma variables. These findings suggest that genetic variants at the VDR locus may play a role in acute wheeze/asthma severity in children.

中文翻译：

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维生素D受体多态性与儿童喘息疾病的严重程度和哮喘加重有关。

在多个队列研究中，维生素D受体（VDR）基因的单核苷酸多态性（SNPs）已显示出与哮喘发展的关联和关联。但是，大多数研究集中在疾病稳定的人群中的哮喘表型。我们调查了一组澳大利亚儿童的VDR SNPs与喘息/哮喘急性发作频率和严重程度之间的关系，因为识别出有可能患上更严重病情的儿童的能力可能会导致个性化和改良的基因型特异性治疗途径。我们成功地将657例儿童的VDR基因的5个SNPs基因型（rs2525046，rs9729，rs1544410（BsmI），rs22239179和rs2228570（FokI））进行了基因分型，这些儿童就诊于患有哮喘，细支气管炎或喘息性疾病的三级儿童医院。使用多元回归分析了VDR SNP与病情加重程度评分，β2-激动剂的使用以及呼吸病加重频率之间的关系。与CC基因型相比，rs2525046（FokI）CT基因型与更高的VDR mRNA强度水平相关（p = 0.007）。在rs2525046 TT基因型和与CC基因型相比更高的VDR mRNA强度水平之间发现了显着趋势（p = 0.056）。与GG基因型儿童相比，具有rs2228570 AA基因型的儿童病情加重程度评分更高（p = 0.001），β2-激动剂治疗反应更差（6 h：p = 0.009和12 h：p = 0.033）。rs1544410（BsmI）TT基因型患儿与CC基因型患儿的病情加重程度评分较低（p = 0.005）。自出生以来，具有rs2228570 GA基因型的儿童比患有GG基因型的儿童出现呼吸道疾病（p = 0.011）和喘息（p = 0.021）的次数和/或入院次数更多。rs9729，rs2525046和r2239179多态性与急性喘息/哮喘变量之间未发现关联。这些发现表明，VDR基因座的遗传变异可能在儿童急性喘息/哮喘严重程度中起作用。