Association of 25-Hydroxyvitamin D status and genetic variation in the vitamin D metabolic pathway with FEV(1) in the Framingham Heart Study

BACKGROUND: 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. METHODS: We estimated the association between serum 25-hydroxyvitamin D [25(OH)D] and cross-sectional forced expiratory volume in the first second (FEV(1)) in Framingham Heart Study (FHS) Offspring and Third Generation participants and the association between serum 25(OH)D and longitudinal change in FEV(1) 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 FEV(1) in Offspring participants and pursued replication of these findings in a meta-analyzed set of 4 independent cohorts. RESULTS: We found a positive cross-sectional association between 25(OH)D and FEV(1) in FHS Offspring and Third Generation participants (P = 0.004). There was little or no association between 25(OH)D and longitudinal change in FEV(1) 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 FEV(1) (gene-based P < 0.05). The most significantly associated SNP from CYP2R1 had a consistent direction of association with FEV(1) in the meta-analyzed set of replication cohorts, but the association did not reach statistical significance thresholds (P = 0.09). CONCLUSIONS: Serum 25(OH)D status was associated with cross-sectional FEV(1), but not longitudinal change in FEV(1). The inconsistent associations may be driven by differences in the groups studied. CYP2R1 demonstrated a gene-based association with longitudinal change in FEV(1) and is a promising candidate gene for further studies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12931-015-0238-y) contains supplementary material, which is available to authorized users.