title: Vitamin D related genes in lung development and asthma pathogenesis.
abstract: BACKGROUND
  Poor maternal vitamin D intake is a risk factor for subsequent childhood asthma, suggesting that in utero changes related to vitamin D responsive genes might play a crucial role in later disease susceptibility. We hypothesized that vitamin D pathway genes are developmentally active in the fetal lung and that these developmental genes would be associated with asthma susceptibility and regulation in asthma.
  
  
  METHODS
  Vitamin D pathway genes were derived from PubMed and Gene Ontology surveys. Principal component analysis was used to identify characteristic lung development genes.
  
  
  RESULTS
  Vitamin D regulated genes were markedly over-represented in normal human (odds ratio OR 2.15, 95% confidence interval CI: 1.69-2.74) and mouse (OR 2.68, 95% CI: 2.12-3.39) developing lung transcriptomes. 38 vitamin D pathway genes were in both developing lung transcriptomes with >63% of genes more highly expressed in the later than earlier stages of development. In immortalized B-cells derived from 95 asthmatics and their unaffected siblings, 12 of the 38 (31.6%) vitamin D pathway lung development genes were significantly differentially expressed (OR 3.00, 95% CI: 1.43-6.21), whereas 11 (29%) genes were significantly differentially expressed in 43 control versus vitamin D treated immortalized B-cells from Childhood Asthma Management Program subjects (OR 2.62, 95% CI: 1.22-5.50). 4 genes, LAMP3, PIP5K1B, SCARB2 and TXNIP were identified in both groups; each displays significant biologic plausibility for a role in asthma.
  
  
  CONCLUSIONS
  Our findings demonstrate a significant association between early lung development and asthma-related phenotypes for vitamin D pathway genes, supporting a genomic mechanistic basis for the epidemiologic observations relating maternal vitamin D intake and childhood asthma susceptibility.
authors.forename: Alvin T
authors.initials: AT
authors.lastname: Kho
authors.forename: Sunita
authors.initials: S
authors.lastname: Sharma
authors.forename: Weiliang
authors.initials: W
authors.lastname: Qiu
authors.forename: Roger
authors.initials: R
authors.lastname: Gaedigk
authors.forename: Barbara
authors.initials: B
authors.lastname: Klanderman
authors.forename: Simin
authors.initials: S
authors.lastname: Niu
authors.forename: Chris
authors.initials: C
authors.lastname: Anderson
authors.forename: James S
authors.initials: JS
authors.lastname: Leeder
authors.forename: Scott T
authors.initials: ST
authors.lastname: Weiss
authors.affiliation: Harvard Medical School, Boston, MA, USA. kelan.tantisira@channing.harvard.edu.
authors.forename: Kelan G
authors.initials: KG
authors.lastname: Tantisira
mesh_terms: D000818:Animals; D001249:Asthma / Q000209:etiology* / Q000235:genetics*; D002460:Cell Line; D002648:Child; D019295:Computational Biology; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008168:Lung / Q000254:growth & development*; D051379:Mice; D014807:Vitamin D / Q000378:metabolism*
chemical_list: D014807:Vitamin D