Open Access Research article

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

Brian J Reardon1, Joyanna G Hansen1, Ronald G Crystal2, Denise K Houston3, Stephen B Kritchevsky3, Tamara Harris4, Kurt Lohman5, Yongmei Liu6, George T O’Connor78, Jemma B Wilk89, Jason Mezey1011, Chuan Gao10 and Patricia A Cassano112*

  • * Corresponding author: Patricia A Cassano

  • † Equal contributors

Author Affiliations

1 Division of Nutritional Sciences, Cornell University, 209 Savage Hall, Ithaca, NY 14853, USA

2 Department of Genetic Medicine, Weill Cornell Medical College, New York, NY, USA

3 Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA

4 Intramural Research Program, National Institute on Aging, Laboratory of Epidemiology, Demography, and Biometry, Gateway Building, 3C309, 7201 Wisconsin Avenue, Bethesda, MD 20892, USA

5 Division of Public Health Sciences, Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA

6 Division of Public Health Sciences, Department of Epidemiology & Prevention, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA

7 Section of Pulmonary, Allergy & Critical Care Medicine, Department of Medicine, Boston University School of Medicine, Boston, MA, USA

8 The National Heart, Lung, and Blood Institute’s Framingham Heart Study, Framingham, MA, USA

9 Division of Aging, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

10 Biological Statistics and Computational Biology, Cornell University, Ithaca, NY 14853, USA

11 Department of Medical Genetics, Weill Cornell Medical College, New York, NY, USA

12 Division of Biostatistics and Epidemiology, Department of Public Health, Weill Cornell Medical College, New York, NY, USA

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BMC Medical Genetics 2013, 14:122  doi:10.1186/1471-2350-14-122

Published: 25 November 2013



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 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.


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.

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