| Genetic variants and associations of 25-hydroxyvitamin D concentrations with major clinical outcomes. | |
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MedLine Citation:
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PMID: 23150009 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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CONTEXT: Lower serum 25-hydroxyvitamin D concentrations are associated with greater risks of many chronic diseases across large, prospective community-based studies. Substrate 25-hydroxyvitamin D must be converted to 1,25-dihydroxyvitamin D for full biological activity, and complex metabolic pathways suggest that interindividual variability in vitamin D metabolism may alter the clinical consequences of measured serum 25-hydroxyvitamin D. OBJECTIVE: To investigate whether common variation within genes encoding the vitamin D-binding protein, megalin, cubilin, CYP27B1, CYP24A1, and the vitamin D receptor (VDR) modify associations of low 25-hydroxyvitamin D with major clinical outcomes. DESIGN, SETTING, AND PARTICIPANTS: Examination of 141 single-nucleotide polymorphisms in a discovery cohort of 1514 white participants (who were recruited from 4 US regions) from the community-based Cardiovascular Health Study. Participants had serum 25-hydroxyvitamin D measurements in 1992-1993 and were followed up for a median of 11 years (through 2006). Replication meta-analyses were conducted across the independent, community-based US Health, Aging, and Body Composition (n = 922; follow-up: 1998-1999 through 2005), Italian Invecchiare in Chianti (n = 835; follow-up: 1998-2000 through 2006), and Swedish Uppsala Longitudinal Study of Adult Men (n = 970; follow-up: 1991-1995 through 2008) cohort studies. MAIN OUTCOME MEASURE: Composite outcome of incident hip facture, myocardial infarction, cancer, and mortality over long-term follow-up. RESULTS: Interactions between 5 single-nucleotide polymorphisms and low 25-hydroxyvitamin D concentration were identified in the discovery phase and 1 involving a variant in the VDR gene replicated in independent meta-analysis. Among Cardiovascular Health Study participants, low 25-hydroxyvitamin D concentration was associated with hazard ratios for risk of the composite outcome of 1.40 (95% CI, 1.12-1.74) for those who had 1 minor allele at rs7968585 and 1.82 (95% CI, 1.31-2.54) for those with 2 minor alleles at rs7968585. In contrast, there was no evidence of an association (estimated hazard ratio, 0.93 [95% CI, 0.70-1.24]) among participants who had 0 minor alleles at this single-nucleotide polymorphism. CONCLUSION: Known associations of low 25-hydroxyvitamin D with major health outcomes may vary according to common genetic differences in the vitamin D receptor. |
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Authors:
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Gregory P Levin; Cassianne Robinson-Cohen; Ian H de Boer; Denise K Houston; Kurt Lohman; Yongmei Liu; Stephen B Kritchevsky; Jane A Cauley; Toshiko Tanaka; Luigi Ferrucci; Stefania Bandinelli; Kushang V Patel; Emil Hagström; Karl Michaëlsson; Håkan Melhus; Thomas Wang; Myles Wolf; Bruce M Psaty; David Siscovick; Bryan Kestenbaum |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: JAMA : the journal of the American Medical Association Volume: 308 ISSN: 1538-3598 ISO Abbreviation: JAMA Publication Date: 2012 Nov |
Date Detail:
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Created Date: 2012-11-15 Completed Date: 2012-11-20 Revised Date: 2013-05-20 |
Medline Journal Info:
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Nlm Unique ID: 7501160 Medline TA: JAMA Country: United States |
Other Details:
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Languages: eng Pagination: 1898-905 Citation Subset: AIM; IM |
Affiliation:
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Department of Biostatistics, University of Washington, Seattle, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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25-Hydroxyvitamin D3 1-alpha-Hydroxylase
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genetics Aged Chronic Disease / mortality* Cohort Studies Female Genetic Variation* Genotype Hip Fractures / mortality Humans Low Density Lipoprotein Receptor-Related Protein-2 / genetics Male Meta-Analysis as Topic Myocardial Infarction / mortality Neoplasms / mortality Polymorphism, Single Nucleotide Receptors, Calcitriol / genetics* Receptors, Cell Surface / genetics Risk Steroid Hydroxylases / genetics Vitamin D / analogs & derivatives*, blood, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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263 MD 821336/MD/NIMHD NIH HHS; 263 MD9164/MD/NIMHD NIH HHS; DK063491/DK/NIDDK NIH HHS; HHSN268200782096C//PHS HHS; HHSN268201200036C//PHS HHS; HL087652/HL/NHLBI NIH HHS; HL096875/HL/NHLBI NIH HHS; K01 AG030506/AG/NIA NIH HHS; KL2 TR000421/TR/NCATS NIH HHS; M01RR00069/RR/NCRR NIH HHS; N.1-AG-1-1/AG/NIA NIH HHS; N.1-AG-1-2111/AG/NIA NIH HHS; N01 HC-15103/HC/NHLBI NIH HHS; N01 HC-55222/HC/NHLBI NIH HHS; N01-AG-5-0002/AG/NIA NIH HHS; N01-HC-35129/HC/NHLBI NIH HHS; N01-HC-45133/HC/NHLBI NIH HHS; N01-HC-75150/HC/NHLBI NIH HHS; N01-HC-85079/HC/NHLBI NIH HHS; N01-HC-85086/HC/NHLBI NIH HHS; N01AG62101/AG/NIA NIH HHS; N01AG62103/AG/NIA NIH HHS; N01AG62106/AG/NIA NIH HHS; R01 AG029364/AG/NIA NIH HHS; R01 HL084443/HL/NHLBI NIH HHS; R01 HL096875/HL/NHLBI NIH HHS; R01-AG029364/AG/NIA NIH HHS; R01-AG032098/AG/NIA NIH HHS; R01AG027002/AG/NIA NIH HHS; U01 HL080295/HL/NHLBI NIH HHS; UL1 TR000423/TR/NCATS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Low Density Lipoprotein Receptor-Related Protein-2; 0/Receptors, Calcitriol; 0/Receptors, Cell Surface; 0/intrinsic factor-cobalamin receptor; 1406-16-2/Vitamin D; 64719-49-9/25-hydroxyvitamin D; EC 1.14.-/25-Hydroxyvitamin D3 1-alpha-Hydroxylase; EC 1.14.-/Steroid Hydroxylases; EC 1.14.13.-/vitamin D 24-hydroxylase |
| Comments/Corrections | |
Comment In:
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JAMA. 2013 Mar 6;309(9):872-3
[PMID:
23462776
]
JAMA. 2013 Mar 6;309(9):873 [PMID: 23462777 ] |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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