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Vitamin D-binding protein haplotype is associated with hospitalization for RSV bronchiolitis

机译：维生素D结合蛋白单倍型与RSV毛细支气管炎的住院治疗相关

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Background: Between 75 000 and 125 000 U.S. infants are hospitalized for respiratory syncytial virus (RSV) bronchiolitis every year. Up to half will be diagnosed with asthma in later childhood. Vitamin D deficiency has been associated with susceptibility to asthma and respiratory infections. Measured vitamin D is largely bound to vitamin D-binding protein (VDBP); VDBP levels are influenced by its gene (GC) haplotype. Objective: We assessed the relationship between polymorphisms rs7041 and rs4588, which define haplotypes GC1s, GC1f, and GC2, and RSV bronchiolitis susceptibility and subsequent asthma. Methods: We retrospectively recruited 198 otherwise healthy children (93% White) hospitalized for severe RSV bronchiolitis in Boston and 333 parents into a follow-up study to assess asthma diagnosis. Data were analysed using family-based genetic association tests. We independently validated our results in 465 White children hospitalized with RSV bronchiolitis and 930 White population controls from the Netherlands. Results: The rs7041_C allele (denoting haplotype GC1s) was overtransmitted (P = 0.02, additive model) in the entire Boston cohort, in Whites (P = 0.03), and especially in children subsequently diagnosed with asthma (P = 0.006). The GC1f haplotype was undertransmitted in the asthma subgroups (all races and White, both P < 0.05). The rs7041_C allele was also more frequent in the RSV bronchiolitis group compared with controls (OR 1.12, 95% CI 1.02, 1.4, P = 0.03) in the Netherlands, especially in mechanically ventilated patients (P = 0.009). Conclusion and Clinical Relevance: GC1s haplotype carriage may increase the risk of RSV bronchiolitis in infancy and subsequent asthma development. The GC1s haplotype is associated with higher VDBP levels, resulting in less freely available vitamin D. Key Messages: Vitamin D-binding protein (VDBP) haplotypes influence free vitamin D levels. We report an association between a VDBP haplotype and hospitalization for RSV bronchiolitis in infancy in two independent cohorts.
机译：背景：每年有75 000至125 000美国婴儿因呼吸道合胞病毒（RSV）细支气管炎住院。在儿童后期，最多有一半将被诊断出患有哮喘。维生素D缺乏与哮喘和呼吸道感染易感性有关。测得的维生素D在很大程度上与维生素D结合蛋白（VDBP）结合; VDBP水平受其基因（GC）单倍型的影响。目的：我们评估了定义单倍型GC1s，GC1f和GC2的多态性rs7041和rs4588与RSV细支气管炎易感性和随后哮喘的关系。方法：我们回顾性研究了198例在波士顿因严重RSV细支气管炎住院的健康儿童（93％的白人）和333名父母，进行了一项随访研究以评估哮喘的诊断。使用基于家庭的遗传关联测试分析数据。我们对来自荷兰的465名因RSV毛细支气管炎住院的白人儿童和930名来自白人的对照组进行了独立的验证。结果：在整个波士顿队列中，在白人中，rs7041_C等位基因（表示单倍型GC1）被过度传播（P = 0.02，加性模型）（P = 0.03），尤其是在后来被诊断患有哮喘的儿童中（P = 0.006）。在哮喘亚组中，GC1f单体型传播不足（所有种族和白人，均P <0.05）。与荷兰的对照组（OR 1.12，95％CI 1.02，1.4，P = 0.03）相比，RSV细支气管炎组中的rs7041_C等位基因也更为常见，尤其是在机械通气患者中（P = 0.009）。结论和临床意义：GC1单倍型携带可能增加婴儿期及随后哮喘发展中RSV细支气管炎的风险。 GC1的单倍型与较高的VDBP水平相关，从而导致游离D的自由利用量减少。重要信息：维生素D结合蛋白（VDBP）的单倍型会影响自由维生素D的水平。我们报告了两个独立队列中婴儿期RSV细支气管炎的VDBP单倍型与住院之间的关联。

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