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Published on: December 10, 2013
Vitamin D-binding protein haplotype is associated with hospitalization for RSV bronchiolitis
A G Randolph1, W-K Yip, K Falkenstein-Hagander
1Department 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.
Insights
A specific vitamin D-binding protein (VDBP) gene variant, GC1s, is linked to increased risk of respiratory syncytial virus (RSV) bronchiolitis in infants. This genetic factor may also contribute to the development of childhood asthma.
Area of Science:
- Genetics
- Immunology
- Pediatrics
Background:
- Respiratory syncytial virus (RSV) bronchiolitis hospitalizes 75,000-125,000 U.S. infants annually, with up to half developing asthma later.
- Vitamin D deficiency is associated with increased susceptibility to asthma and respiratory infections.
- Vitamin D-binding protein (VDBP) levels, influenced by its gene (GC) haplotype, affect vitamin D availability.
Purpose of the Study:
- To investigate the association between specific VDBP gene polymorphisms (rs7041 and rs4588) and their haplotypes (GC1s, GC1f, GC2) with RSV bronchiolitis susceptibility.
- To determine if these VDBP genetic variations are linked to the subsequent development of asthma in children.
Main Methods:
- Retrospective recruitment of 198 infants hospitalized for severe RSV bronchiolitis and 333 parents for asthma follow-up in Boston.
- Utilized family-based genetic association tests for data analysis.
- Independent validation in 465 White children hospitalized with RSV bronchiolitis and 930 White population controls from the Netherlands.
Main Results:
- The rs7041_C allele, defining the GC1s haplotype, was significantly overtransmitted in the Boston cohort, particularly in children later diagnosed with asthma (P=0.006).
- The GC1f haplotype was undertransmitted in asthma subgroups.
- In the Netherlands cohort, the rs7041_C allele was more frequent in RSV bronchiolitis patients (OR 1.12) versus controls, especially in those requiring mechanical ventilation (P=0.009).
Conclusions:
- Carriage of the GC1s VDBP haplotype may elevate the risk of infantile RSV bronchiolitis and subsequent asthma development.
- The GC1s haplotype is associated with higher VDBP levels, potentially reducing the amount of free vitamin D available.
- These findings highlight the role of VDBP haplotypes in influencing free vitamin D levels and link a specific VDBP haplotype to RSV bronchiolitis hospitalization.
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.
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