BackgroundVitamin 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.MethodsWe 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.ResultsWe 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).ConclusionsSerum 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-015-0238-y) contains supplementary material, which is available to authorized users.

The new recommended nutrient intakes (RNI) of vitamin A published by FAO/WHO [1] are twotiered (table 1), with a basal level, corresponding to a recommended intake to prevent deficiency, and a safe level, similar to the recommended dietary allowance (RDA) set for the United States [2], which corresponds to an intake recommended for adequate liver storage of the vitamin [1,3,4] The dietary sources of vitamin A are of two categories: vitamin A. or retinol, also known as preformed vitamin A; and provitamin A, which refers to those carotenoid precursors that are biologically active as retinol. TABLE 1. Recommended dietary intakes of vitamin A (RE) Basal Safe Infants 180 350 Children

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