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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.
Tuesday,2015-10-06 13:46 America/Los_Angeles — zdrager
| Title | Association of 25-Hydroxyvitamin D status and genetic variation in the vitamin D metabolic pathway with FEV1 in the Framingham Heart Study. |
| Publication Type | Journal Article |
| Year of Publication | 2015 |
| Authors | 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, Cassano, PA |
| Corporate/Institutional Authors | SUNLIGHT Consortium |
| Journal | Respir Res |
| Volume | 16 |
| Pagination | 81 |
| Date Published | 2015 |
| ISSN | 1465-993X |
| Keywords | Adult, Aged, Cohort Studies, Cross-Sectional Studies, DNA-Binding Proteins, Female, Genetic Variation, Humans, Longitudinal Studies, Male, Massachusetts, Metabolic Networks and Pathways, Middle Aged, Nuclear Proteins, Polymorphism, Single Nucleotide, Vitamin D |
| Abstract | <p><b>BACKGROUND: </b>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.</p><p><b>METHODS: </b>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.</p><p><b>RESULTS: </b>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).</p><p><b>CONCLUSIONS: </b>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.</p> |
| DOI | 10.1186/s12931-015-0238-y |
| Alternate Journal | Respir. Res. |
| PubMed ID | 26122139 |
| PubMed Central ID | PMC4491260 |
| Grant List | 1R01AG032098-01A1 / AG / NIA NIH HHS / United States AG023629 / AG / NIA NIH HHS / United States AG14759 / AG / NIA NIH HHS / United States DK063491 / DK / NIDDK NIH HHS / United States HHSN268200782096C / / PHS HHS / United States HHSN268200800007C / / PHS HHS / United States HHSN268201200036C / / PHS HHS / United States HL080295 / HL / NHLBI NIH HHS / United States HL087652 / HL / NHLBI NIH HHS / United States HL105756 / HL / NHLBI NIH HHS / United States N01-HC-05187 / HC / NHLBI NIH HHS / United States N01-HC-25195 / HC / NHLBI NIH HHS / United States N01-HC-45134 / HC / NHLBI NIH HHS / United States N01-HC-45204 / HC / NHLBI NIH HHS / United States N01-HC-45205 / HC / NHLBI NIH HHS / United States N01-HC-48047 / HC / NHLBI NIH HHS / United States N01-HC-48048 / HC / NHLBI NIH HHS / United States N01-HC-48049 / HC / NHLBI NIH HHS / United States N01-HC-48050 / HC / NHLBI NIH HHS / United States N01-HC-95095 / HC / NHLBI NIH HHS / United States N01AG2103 / AG / NIA NIH HHS / United States N01AG62101 / AG / NIA NIH HHS / United States N01AG62106 / AG / NIA NIH HHS / United States N01HC55222 / HC / NHLBI NIH HHS / United States N01HC85079 / HC / NHLBI NIH HHS / United States N01HC85080 / HC / NHLBI NIH HHS / United States N01HC85081 / HC / NHLBI NIH HHS / United States N01HC85082 / HC / NHLBI NIH HHS / United States N01HC85083 / HC / NHLBI NIH HHS / United States N01HC85086 / HC / NHLBI NIH HHS / United States N02-HL-6-4278 / HL / NHLBI NIH HHS / United States R01-AG028050 / AG / NIA NIH HHS / United States R01-HL-084099 / HL / NHLBI NIH HHS / United States R01-NR012459 / NR / NINR NIH HHS / United States RC1AG035835 / AG / NIA NIH HHS / United States T32-DK-7158-36 / DK / NIDDK NIH HHS / United States U01-HG-004424 / HG / NHGRI NIH HHS / United States U01-HG-004446 / HG / NHGRI NIH HHS / United States U01-HG-004729 / HG / NHGRI NIH HHS / United States UL1TR000124 / TR / NCATS NIH HHS / United States / / Intramural NIH HHS / United States |