Vitamin D-responsive SGPP2 variants associated with lung cell expression and lung function. Academic Article uri icon

Overview

MeSH

  • African Americans
  • Aged
  • Aging
  • Body Composition
  • Cohort Studies
  • Epithelial Cells
  • European Continental Ancestry Group
  • Female
  • Forced Expiratory Volume
  • Humans
  • Male
  • Oligonucleotide Array Sequence Analysis
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Quantitative Trait Loci
  • Respiratory Function Tests
  • Vitamin D

MeSH Major

  • Lung
  • Membrane Proteins
  • Phosphoric Monoester Hydrolases

abstract

  • 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. 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). 13 candidate genes had significant differences in expression by serum 25(OH)D (nominal pā€‰<ā€‰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. 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 date

  • 2013

has subject area

  • African Americans
  • Aged
  • Aging
  • Body Composition
  • Cohort Studies
  • Epithelial Cells
  • European Continental Ancestry Group
  • Female
  • Forced Expiratory Volume
  • Humans
  • Lung
  • Male
  • Membrane Proteins
  • Oligonucleotide Array Sequence Analysis
  • Phenotype
  • Phosphoric Monoester Hydrolases
  • Polymorphism, Single Nucleotide
  • Quantitative Trait Loci
  • Respiratory Function Tests
  • Vitamin D

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3907038

Digital Object Identifier (DOI)

  • 10.1186/1471-2350-14-122

PubMed ID

  • 24274704

Additional Document Info

start page

  • 122

volume

  • 14