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

Hansen JG, Gao W, Dupuis J, O'Connor GT, Tang W, Kowgier M, Sood A, Gharib SA, Palmer LJ, Fornage M, Heckbert SR, Psaty BM, Booth SL, SUNLIGHT ConsortiumCassano PA - Respir. Res. (2015)

Bottom Line: 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.The inconsistent associations may be driven by differences in the groups studied.

View Article: PubMed Central - PubMed

Affiliation: Division of Nutritional Sciences, Cornell University, 209 Savage Hall, Ithaca, NY, 14853, USA. jg553@cornell.edu.

ABSTRACT

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 (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.

Results: 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).

Conclusions: 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.

No MeSH data available.


Related in: MedlinePlus

Spline analysis of log-transformed 25(OH) D by residual FEV1
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Fig1: Spline analysis of log-transformed 25(OH) D by residual FEV1

Mentions: 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 1-unit increase in log-transformed 25(OH)D was associated with a 45 mL increase in FEV1 (P = 0.004) (Table 3). A consistent direction of association was observed for the dichotomous vitamin D variable at thresholds of <12 ng/mL or <20 ng/mL, using the Institute of Medicine thresholds for risk of vitamin D deficiency and inadequacy, respectively [3], but coefficients for the dichotomous serum vitamin D variables did not reach the significance threshold of P < 0.05. The spline analysis estimating the cross-sectional serum 25(OH)D—FEV1 association showed an approximately linear, positive association for serum 25(OH)D < 12 ng/mL. In the 12 to 40 ng/mL range, the serum 25(OH)D—FEV1 association attenuated, and a plateau was reached above a threshold of about 40 ng/mL (Fig. 1). The pattern of association did not differ between Offspring and Third Generation participants (sub panels of Fig. 1), and the estimates of the linear serum 25(OH)D—FEV1 association were about the same in both cohorts (beta coefficient for serum 25(OH)D—FEV1 association was 37 (SE: 29, P = 0.20) and 34 (SE: 19, P = 0.08) mL in Offspring and Third Generation, respectively).Table 3


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

Hansen JG, Gao W, Dupuis J, O'Connor GT, Tang W, Kowgier M, Sood A, Gharib SA, Palmer LJ, Fornage M, Heckbert SR, Psaty BM, Booth SL, SUNLIGHT ConsortiumCassano PA - Respir. Res. (2015)

Spline analysis of log-transformed 25(OH) D by residual FEV1
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4491260&req=5

Fig1: Spline analysis of log-transformed 25(OH) D by residual FEV1
Mentions: 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 1-unit increase in log-transformed 25(OH)D was associated with a 45 mL increase in FEV1 (P = 0.004) (Table 3). A consistent direction of association was observed for the dichotomous vitamin D variable at thresholds of <12 ng/mL or <20 ng/mL, using the Institute of Medicine thresholds for risk of vitamin D deficiency and inadequacy, respectively [3], but coefficients for the dichotomous serum vitamin D variables did not reach the significance threshold of P < 0.05. The spline analysis estimating the cross-sectional serum 25(OH)D—FEV1 association showed an approximately linear, positive association for serum 25(OH)D < 12 ng/mL. In the 12 to 40 ng/mL range, the serum 25(OH)D—FEV1 association attenuated, and a plateau was reached above a threshold of about 40 ng/mL (Fig. 1). The pattern of association did not differ between Offspring and Third Generation participants (sub panels of Fig. 1), and the estimates of the linear serum 25(OH)D—FEV1 association were about the same in both cohorts (beta coefficient for serum 25(OH)D—FEV1 association was 37 (SE: 29, P = 0.20) and 34 (SE: 19, P = 0.08) mL in Offspring and Third Generation, respectively).Table 3

Bottom Line: 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.The inconsistent associations may be driven by differences in the groups studied.

View Article: PubMed Central - PubMed

Affiliation: Division of Nutritional Sciences, Cornell University, 209 Savage Hall, Ithaca, NY, 14853, USA. jg553@cornell.edu.

ABSTRACT

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 (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.

Results: 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).

Conclusions: 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.

No MeSH data available.


Related in: MedlinePlus