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

Brian J. Reardon, Joyanna G. Hansen, Ronald G. Crystal, Denise K. Houston, Stephen B. Kritchevsky, Tamara Harris, Kurt Lohman, Yongmei Liu, George T. O'Connor, Jemma B. Wilk, Jason Mezey, Chuan Gao, Patricia A. Cassano

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


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.

Original languageEnglish (US)
Article number122
JournalBMC Medical Genetics
Issue number1
StatePublished - Nov 25 2013
Externally publishedYes


  • Airflow obstruction
  • FEV1
  • FEV1/FVC
  • SGPP2
  • Vitamin D

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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