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


CONCLUSIONS
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.


CONCLUSIONS
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.
Department of Anesthesia, Perioperative and Pain Medicine, Boston Children's Hospital, Boston, MA, USA; Channing, Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
A G
AG
Randolph
W-K
WK
Yip
K
K
Falkenstein-Hagander
S T
ST
Weiss
R
R
Janssen
S
S
Keisling
L
L
Bont
D001990:Bronchiolitis, Viral / Q000097:blood / Q000453:epidemiology / Q000235:genetics* / Q000628:therapy; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006239:Haplotypes; D006760:Hospitalization; D006801:Humans; D007223:Infant; D008297:Male; D020641:Polymorphism, Single Nucleotide; D018357:Respiratory Syncytial Virus Infections / Q000097:blood / Q000453:epidemiology / Q000235:genetics* / Q000628:therapy; D018113:Respiratory Syncytial Virus, Human; D012189:Retrospective Studies; D014807:Vitamin D / Q000097:blood; D014809:Vitamin D-Binding Protein / Q000097:blood / Q000235:genetics*
D014809:Vitamin D-Binding Protein; D014807:Vitamin D
GC; RSV; asthma; bronchiolitis; children; haplotype; infants; polymorphisms; vitamin D; vitamin D-binding protein