Abstract
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.
Highlights
Decreased lung function due to airflow obstruction is the primary characteristic of chronic obstructive pulmonary disease (COPD), the 3rd leading cause of mortality in the United States [1]
We pursued replication of the single nucleotide polymorphisms (SNPs) findings in four independent epidemiologic cohort studies, namely the Health, Aging and Body Composition Study (Health ABC), the Coronary Artery Risk Development in Young Adults Study (CARDIA), the Busselton Health Study (BHS), and the Cardiovascular Health Study (CHS), and we investigated the SNPs in relation to serum 25(OH)D status in the SUNLIGHT consortium [6]
25(OH)D associations with cross-sectional FEV1 and rate of change in FEV1 25(OH)D was positively associated with FEV1 in the cross-sectional analysis of the combined sample of Offspring and Third Generation participants, such that a 1unit increase in log-transformed 25(OH)D was associated with a 45 mL increase in FEV1 (P = 0.004) (Table 3)
Summary
Decreased lung function due to airflow obstruction is the primary characteristic of chronic obstructive pulmonary disease (COPD), the 3rd leading cause of mortality in the United States [1]. Several cross-sectional, population-based observational studies have demonstrated strong, positive associations between vitamin D levels and lung function [11,12,13], one study in the Hertfordshire cohort did not replicate cross-sectional associations [14]. A recent cohort study demonstrated that low serum vitamin D was associated both with steeper lung function decline and a higher risk of developing COPD [20]. An observational study in COPD patients reported no association between serum 25(OH)D and longitudinal lung outcomes [21], but a recent population-based study in an elderly male cohort reported steeper lung function decline in current smokers with serum 25(OH)D ≤20 ng/mL versus smokers with higher 25(OH)D [22]. 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
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