Premium
Vitamin D ‐binding protein haplotype is associated with hospitalization for RSV bronchiolitis
Author(s) -
Randolph A. G.,
Yip W.K.,
FalkensteinHagander K.,
Weiss S. T.,
Janssen R.,
Keisling S.,
Bont L.
Publication year - 2014
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.12247
Subject(s) - bronchiolitis , haplotype , asthma , vitamin d and neurology , medicine , immunology , cohort , allele , vitamin d deficiency , respiratory system , biology , gene , genetics
Summary 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 GC 1s, GC 1f, and GC 2, 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 GC 1s) 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 GC 1f 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 GC 1s haplotype carriage may increase the risk of RSV bronchiolitis in infancy and subsequent asthma development. The GC 1s 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.