Vitamin D-binding protein haplotype is associated with hospitalization for RSV bronchiolitis.
Vitamin D-binding protein haplotype is associated with hospitalization for RSV bronchiolitis.
复制标题
维生素 D 结合蛋白单倍型与 RSV 细支气管炎住院相关。
DOI：
10.1111/cea.12247
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Bont,L
中科院分区：
文献类型：
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作者：
Randolph,AG;Yip,W-K;Falkenstein-Hagander,K;Weiss,ST;Janssen,R;Keisling,S;Bont,L
背景美国每年有75,000至125,000名婴儿因呼吸道合胞病毒(RSV)毛细支气管炎而住院。多达一半的儿童将在儿童后期被诊断为哮喘。维生素D缺乏与哮喘和呼吸道感染的易感性有关。目的探讨单倍型rs7041和rs4588与呼吸道合胞病毒毛细支气管炎易感性和继发性哮喘的关系。方法我们回顾招募了198名波士顿地区因呼吸道合胞病毒毛细支气管炎住院的健康儿童(93%为白人)和333名父母进行随访，以评估哮喘的诊断。使用基于家庭的基因关联测试对数据进行分析。结果rs7041_C等位基因(表示单倍型GC1S)在整个波士顿队列中、在白人中(P=0.03)、特别是在后来诊断为哮喘的儿童中(P=0.03)是过度传播的(P=0.02，加性模型)。GC1f单倍型在哮喘亚组(所有种族和白人，均为P<；)中传播不足。在荷兰，RSV毛细支气管炎组rs7041_C等位基因频率也高于对照组(OR1.12，95%CI1.02，1.4，P=0.03)，尤其是在机械通气组(P=0.03)。结论和临床相关性GC1S单倍型携带者可能增加婴儿期呼吸道合胞病毒毛细支气管炎和继发哮喘的风险。GC1S单倍型与较高的VDBP水平相关，导致可自由获得的维生素D较少。关键信息维生素D结合蛋白(VDBP)单倍型影响游离维生素D水平。我们在两个独立的队列中报告了VDBP单倍型与婴儿期呼吸道合胞病毒毛细支气管炎住院之间的关联。
BackgroundBetween 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.ObjectiveWe assessed the relationship between polymorphisms rs7041 and rs4588, which define haplotypes GC1s, GC1f, and GC2, and RSV bronchiolitis susceptibility and subsequent asthma.MethodsWe 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.ResultsThe 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, bothP< 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 RelevanceGC1s 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 MessagesVitamin 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.