Vitamin D related genes in lung development and asthma pathogenesis

• Published in: BMC medical genomics Vol. 6; no. 1; p. 47
• Main Authors: Kho, Alvin T, Sharma, Sunita, Qiu, Weiliang, Gaedigk, Roger, Klanderman, Barbara, Niu, Simin, Anderson, Chris, Leeder, James S, Weiss, Scott T, Tantisira, Kelan G
• Format: Journal Article
• Language: English
• Published: London BioMed Central 05.11.2013; BioMed Central Ltd
• Subjects: Alfacalcidol; Animals; Asthma; Asthma - etiology; Asthma - genetics; Asthma in children; Bioinformatic and algorithmical studies; Biomedical and Life Sciences; Biomedicine; Calcifediol; Cell Line; Child; Children & youth; Colleges & universities; Computational Biology; Confidence intervals; Disease; Disease susceptibility; Gene Expression; Gene Expression Profiling; Genes; Genetic aspects; Genetic Predisposition to Disease - genetics; Genomes; Hospitals; Human Genetics; Humans; Hypotheses; Laboratory animals; Lung - growth & development; Mice; Microarrays; Ontology; Pediatrics; Physiological aspects; Pregnancy; Principal components analysis; Research Article; Risk factors; Vitamin D; Vitamin D - metabolism; Vitamin deficiency; Womens health; World Asthma Day 2014: recent insights into asthma; Writing; United States; Kansas City Missouri; Lung development; Vitamin D; Cholecalciferol; Fetal programming; Asthma
• ISSN: 1755-8794; 1755-8794
• DOI: 10.1186/1755-8794-6-47

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.