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

BMC Medical Genetics

Patricia A Cassano⁷  Chuan Gao^1,10  Jason Mezey²  Jemma B Wilk⁵  George T O’Connor¹  Yongmei Liu³  Kurt Lohman^1,11  Tamara Harris⁴  Stephen B Kritchevsky⁶  Denise K Houston⁶  Ronald G Crystal⁹  Joyanna G Hansen⁸  Brian J Reardon⁸ 

[1] The National Heart, Lung, and Blood Institute’s Framingham Heart Study, Framingham, MA, USA;Department of Medical Genetics, Weill Cornell Medical College, New York, NY, USA;Division of Public Health Sciences, Department of Epidemiology & Prevention, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA;Intramural Research Program, National Institute on Aging, Laboratory of Epidemiology, Demography, and Biometry, Gateway Building, 3C309, 7201 Wisconsin Avenue, Bethesda, MD 20892, USA;Division of Aging, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA;Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA;Division of Biostatistics and Epidemiology, Department of Public Health, Weill Cornell Medical College, New York, NY, USA;Division of Nutritional Sciences, Cornell University, 209 Savage Hall, Ithaca, NY 14853, USA;Department of Genetic Medicine, Weill Cornell Medical College, New York, NY, USA;Biological Statistics and Computational Biology, Cornell University, Ithaca, NY 14853, USA;Division of Public Health Sciences, Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA

关键词: FEV₁/FVC;    SGPP2;    FEV₁;    Airflow obstruction;    Vitamin D;   

Others  :  1122572
DOI  :  10.1186/1471-2350-14-122

 received in 2013-01-21, accepted in 2013-11-08,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Reardon et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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