A G Randolph1, W-K Yip, K Falkenstein-Hagander, S T Weiss, R Janssen, S Keisling, L Bont. 1. 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.
Abstract
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.
RCT Entities:
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.
Authors: James M Stark; Susan A McDowell; Vincent Koenigsknecht; Daniel R Prows; John E Leikauf; Ann Marie Le Vine; George D Leikauf Journal: J Med Virol Date: 2002-05 Impact factor: 2.327
Authors: Tina E Faber; Annemieke Schuurhof; Annelies Vonk; Gerard H Koppelman; Marije P Hennus; Jan L L Kimpen; Riny Janssen; Louis J Bont Journal: PLoS One Date: 2012-05-04 Impact factor: 3.240
Authors: Gloria Moreno-Solís; Fernando Fernández-Gutiérrez; Javier Torres-Borrego; Ricardo Torcello-Gáspar; José Luis Gómez-Chaparro Moreno; Juan Luis Pérez-Navero Journal: Eur J Pediatr Date: 2014-09-02 Impact factor: 3.183
Authors: Eric A F Simões; John P DeVincenzo; Michael Boeckh; Louis Bont; James E Crowe; Paul Griffiths; Frederick G Hayden; Richard L Hodinka; Rosalind L Smyth; Keith Spencer; Steffen Thirstrup; Edward E Walsh; Richard J Whitley Journal: J Infect Dis Date: 2015-03-15 Impact factor: 5.226
Authors: Wanda G H Han; Hennie M Hodemaekers; Bhawani Nagarajah; Martien M C Poelen; Kina Helm; Riny Janssen; Cécile A C M van Els Journal: PLoS One Date: 2016-02-19 Impact factor: 3.240
Authors: Jonatan J Carvajal; Andrea M Avellaneda; Camila Salazar-Ardiles; Jorge E Maya; Alexis M Kalergis; Margarita K Lay Journal: Front Immunol Date: 2019-09-12 Impact factor: 7.561
Authors: Dara G Torgerson; Tusar Giri; Todd E Druley; Jie Zheng; Scott Huntsman; Max A Seibold; Andrew L Young; Toni Schweiger; Huiqing Yin-Declue; Geneline D Sajol; Kenneth B Schechtman; Ryan D Hernandez; Adrienne G Randolph; Leonard B Bacharier; Mario Castro Journal: PLoS One Date: 2015-11-20 Impact factor: 3.240