title: Vitamin D-responsive SGPP2 variants associated with lung cell expression and lung function.
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.
authors.affiliation: Division of Nutritional Sciences, Cornell University, 209 Savage Hall, Ithaca, NY 14853, USA. pac6@cornell.edu.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Reardon
authors.forename: Joyanna G
authors.initials: JG
authors.lastname: Hansen
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Crystal
authors.forename: Denise K
authors.initials: DK
authors.lastname: Houston
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Kritchevsky
authors.forename: Tamara
authors.initials: T
authors.lastname: Harris
authors.forename: Kurt
authors.initials: K
authors.lastname: Lohman
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Liu
authors.forename: George T
authors.initials: GT
authors.lastname: O'Connor
authors.forename: Jemma B
authors.initials: JB
authors.lastname: Wilk
authors.forename: Jason
authors.initials: J
authors.lastname: Mezey
authors.forename: Chuan
authors.initials: C
authors.lastname: Gao
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Cassano
mesh_terms: D001741:Black or African American / Q000235:genetics; D000368:Aged; D000375:Aging; D001823:Body Composition; D015331:Cohort Studies; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D008168:Lung / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D012129:Respiratory Function Tests; D014807:Vitamin D / Q000097:blood; D044465:White People / Q000235:genetics
chemical_list: D008565:Membrane Proteins; D014807:Vitamin D; C498526:SGPP2 protein, human; D010744:Phosphoric Monoester Hydrolases