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Type: Journal article
Title: Association of 25-Hydroxyvitamin D status and genetic variation in the vitamin D metabolic pathway with FEV(1) in the Framingham Heart Study
Author: Hansen, J.G.
Gao, W.
Dupuis, J.
O'Connor, G.T.
Tang, W.
Kowgier, M.
Sood, A.
Gharib, S.A.
Palmer, L.J.
Fornage, M.
Heckbert, S.R.
Psaty, B.M.
Booth, S.L.
Cassano, P.A.
Citation: Respiratory Research, 2015; 16(1):81-1-81-8
Publisher: BioMed Central
Issue Date: 2015
ISSN: 1465-9921
Statement of
JG Hansen, W Gao, J Dupuis, GT O’Connor, W Tang, M Kowgier ... et al.
Abstract: Vitamin D is associated with lung function in cross-sectional studies, and vitamin D inadequacy is hypothesized to play a role in the pathogenesis of chronic obstructive pulmonary disease. Further data are needed to clarify the relation between vitamin D status, genetic variation in vitamin D metabolic genes, and cross-sectional and longitudinal changes in lung function in healthy adults.We estimated the association between serum 25-hydroxyvitamin D [25(OH)D] and cross-sectional forced expiratory volume in the first second (FEV1) in Framingham Heart Study (FHS) Offspring and Third Generation participants and the association between serum 25(OH)D and longitudinal change in FEV1 in Third Generation participants using linear mixed-effects models. Using a gene-based approach, we investigated the association between 241 SNPs in 6 select vitamin D metabolic genes in relation to longitudinal change in FEV1 in Offspring participants and pursued replication of these findings in a meta-analyzed set of 4 independent cohorts.We found a positive cross-sectional association between 25(OH)D and FEV1 in FHS Offspring and Third Generation participants (P=0.004). There was little or no association between 25(OH)D and longitudinal change in FEV1 in Third Generation participants (P=0.97). In Offspring participants, the CYP2R1 gene, hypothesized to influence usual serum 25(OH)D status, was associated with longitudinal change in FEV1 (gene-based P<0.05). The most significantly associated SNP from CYP2R1 had a consistent direction of association with FEV1 in the meta-analyzed set of replication cohorts, but the association did not reach statistical significance thresholds (P=0.09).Serum 25(OH)D status was associated with cross-sectional FEV1, but not longitudinal change in FEV1. The inconsistent associations may be driven by differences in the groups studied. CYP2R1 demonstrated a gene-based association with longitudinal change in FEV1 and is a promising candidate gene for further studies.
Keywords: Vitamin D, 25-hydroxyvitamin D; FEV1; CYP2R1; lung function; Framingham Heart Study
Rights: © Hansen et al. 2015 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.
DOI: 10.1186/s12931-015-0238-y
Grant ID: R01-HL-084099
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