Vitamin D related genes in lung development and asthma pathogenesis

BMC Medical Genomics

Kelan G Tantisira²  Scott T Weiss²  James S Leeder³  Chris Anderson¹  Simin Niu²  Barbara Klanderman²  Roger Gaedigk³  Weiliang Qiu²  Sunita Sharma²  Alvin T Kho⁴ 

[1] University of Rochester Medical Center, Rochester, NY, USA;Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA;Division of Pediatric Clinical Pharmacology and Medical Toxicology, Children’s Mercy Hospital and Clinics, 2401 Gilham Road, Kansas City, MO 64108, USA;Harvard Medical School, Boston, MA, USA

关键词: Fetal programming;    Asthma;    Lung development;    Cholecalciferol;    Vitamin D;   

Others  :  1091561
DOI  :  10.1186/1755-8794-6-47

 received in 2013-06-05, accepted in 2013-10-31,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Kho et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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