Association of 25-Hydroxyvitamin D status and genetic variation in the vitamin D metabolic pathway with FEV1 in the Framingham Heart Study

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.

Large Meta-Analysis in the CHARGE Consortium Provides Evidence For an Association of Serum Vitamin D With Pulmonary Function

“…Our findings show that the association of serum 25(OH)D with FEV 1 and FVC were stronger in 217 magnitude in AA versus EA participants, although the difference by race did not reach statistical 218 significance. The finding may reflect the lower serum 25(OH)D in AA participants, which is 219 consistent with the meta-regression finding and with a previous study reporting attenuated 220 associations at higher serum 25(OH)D (15). Future studies that investigate genetic variation in 221…”

“…The 202 magnitude of the association was about four times greater in the Copenhagen study, which may 203 be due to the difference in the mean serum 25(OH)D (Danish median ~42 nmol/L vs. CHARGE 204 median of ~65 nmol/L) given our finding that the 25(OH)D-PFT association was stronger in 205 cohorts with lower serum 25(OH)D. Our finding for the serum 25(OH)D-FEV 1 association was 206 similar in magnitude to the association reported in a British cohort of 6,789 participants with an 207 average age of 45 years (17) , but weaker than a previous report from the FHS cohort (15) . Given that 208 the rate of decline in FEV 1 at age 45 is increased by ~15 mL/year in current smokers (31) , we 209 estimate that a 10 nmol/L higher 25(OH)D is similar to approximately 1 year of current 210 smoking-related decline in FEV 1 for both ancestries, but in the opposite direction.…”

“…44 Previous observational cross-sectional studies of the vitamin D-pulmonary function association 45 in the general population reported mixed findings. Most of these studies reported a positive 46 association between 25(OH)D and pulmonary function (13)(14)(15)(16)(17)(18)(19) , although some reported a null or 47 inverse association (20)(21)(22) , and two others reported a positive association under certain conditions, 48 such as only in male current smokers (23) or only in overweight and obese males (24) . The largest 49 previous cross-sectional study, which included two Danish cohorts (total n = 18,507), reported 50 positive associations of 25(OH)D with pulmonary function (16) .…”

Vitamin D and Diagnosis of COPD in a Working Population

“…According to an Endocrine Society Clinical Practice Guideline released in the US in 2011 [19], vitamin D insufficiency, defined as 25(OH)D levels of <30 ng/mL, was present in 252 (84.2%) out of 299 epidemiologic studies have proven the possible association between serum levels of 25(OH)D and FEV 1 [14] and it has been reported that vitamin D deficiency is frequently found in subjects with COPD.…”

Vitamin D3 intake modulates diaphragm but not peripheral muscle force in young mice

“…NUMEROUS BENEFICIAL EFFECTS of vitamin D on respiratory health have been reported, including better forced expiratory volume in 1 s (FEV 1 ) (16), decreased asthma susceptibility (31), decreased severity of exacerbations in individuals with chronic obstructive pulmonary disease (COPD) (20), and decreased tuberculosis risk (21). Protective effects may result from a variety of mechanisms including vitamin D-mediated production of antimicrobial peptides, airway remodeling, and modulation of inflammation and immune phenotypes.…”