Vitamin D-responsive SGPP2 variants associated with lung cell expression and lung function.

Publication Type	Academic Article
Authors	Reardon B, Hansen J, Crystal R, Houston D, Kritchevsky S, Harris T, Lohman K, Liu Y, O'Connor G, Wilk J, Mezey J, Gao C, Cassano P
Journal	BMC Med Genet
Volume	14
Pagination	122
Date Published	11/25/2013
ISSN	1471-2350
Keywords	Lung, Membrane Proteins, Phosphoric Monoester Hydrolases
Abstract	BACKGROUND: Vitamin D is associated with lung health in epidemiologic studies, but mechanisms mediating observed associations are poorly understood. This study explores mechanisms for an effect of vitamin D in lung through an in vivo gene expression study, an expression quantitative trait loci (eQTL) analysis in lung tissue, and a population-based cohort study of sequence variants. METHODS: Microarray analysis investigated the association of gene expression in small airway epithelial cells with serum 25(OH)D in adult non-smokers. Sequence variants in candidate genes identified by the microarray were investigated in a lung tissue eQTL database, and also in relation to cross-sectional pulmonary function in the Health, Aging, and Body Composition (Health ABC) study, stratified by race, with replication in the Framingham Heart Study (FHS). RESULTS: 13 candidate genes had significant differences in expression by serum 25(OH)D (nominal p < 0.05), and a genome-wide significant eQTL association was detected for SGPP2. In Health ABC, SGPP2 SNPs were associated with FEV1 in both European- and African-Americans, and the gene-level association was replicated in European-American FHS participants. SNPs in 5 additional candidate genes (DAPK1, FSTL1, KAL1, KCNS3, and RSAD2) were associated with FEV1 in Health ABC participants. CONCLUSIONS: SGPP2, a sphingosine-1-phosphate phosphatase, is a novel vitamin D-responsive gene associated with lung function. The identified associations will need to be followed up in further studies.
DOI	10.1186/1471-2350-14-122
PubMed ID	24274704
PubMed Central ID	PMC3907038