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

BMC Med Genet. 2013 Nov 25:14:122. doi: 10.1186/1471-2350-14-122.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aging
  • Black or African American / genetics
  • Body Composition
  • Cohort Studies
  • Epithelial Cells / metabolism
  • Female
  • Forced Expiratory Volume / physiology
  • Humans
  • Lung / metabolism*
  • Male
  • Membrane Proteins / genetics*
  • Oligonucleotide Array Sequence Analysis
  • Phenotype
  • Phosphoric Monoester Hydrolases / genetics*
  • Polymorphism, Single Nucleotide
  • Quantitative Trait Loci
  • Respiratory Function Tests
  • Vitamin D / blood
  • White People / genetics

Substances

  • Membrane Proteins
  • Vitamin D
  • SGPP2 protein, human
  • Phosphoric Monoester Hydrolases