Vitamin D-binding protein haplotype is associated with hospitalization for RSV bronchiolitis
Article first published online: 22 JAN 2014
© 2013 John Wiley & Sons Ltd
Clinical & Experimental Allergy
Volume 44, Issue 2, pages 231–237, February 2014
How to Cite
Clinical & Experimental Allergy, 2014 (44) 231–237., , , , , and ,
- Issue published online: 22 JAN 2014
- Article first published online: 22 JAN 2014
- Accepted manuscript online: 2 DEC 2013 08:30AM EST
- Manuscript Accepted: 26 NOV 2013
- Manuscript Revised: 20 NOV 2013
- Manuscript Received: 30 APR 2013
- National Institutes of Health (NIH). Grant Number: K23HL04278
- Nathaniel Adamczyk Foundation and MedImmune, Inc.
- GC ;
- RSV ;
- vitamin D;
- vitamin D-binding protein
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.
We assessed the relationship between polymorphisms rs7041 and rs4588, which define haplotypes GC1s, GC1f, and GC2, and RSV bronchiolitis susceptibility and subsequent asthma.
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.
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.
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.