Abstract

Doc number: 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.

Details

Title
Vitamin D-responsive SGPP2 variants associated with lung cell expression and lung function
Author
Reardon, Brian J; Hansen, Joyanna G; Crystal, Ronald G; Houston, Denise K; Kritchevsky, Stephen B; Harris, Tamara; Lohman, Kurt; Liu, Yongmei; O'Connor, George T; Wilk, Jemma B; Mezey, Jason; Gao, Chuan; Cassano, Patricia A
Pages
122
Publication year
2013
Publication date
2013
Publisher
BioMed Central
e-ISSN
14712350
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
1465617781
Copyright
© 2013 Reardon et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.