You are here
Genetic variants and associations of 25-hydroxyvitamin D concentrations with major clinical outcomes.
Monday,2013-01-14 17:01 America/Los_Angeles — poolea2
| Title | Genetic variants and associations of 25-hydroxyvitamin D concentrations with major clinical outcomes. |
| Publication Type | Journal Article |
| Year of Publication | 2012 |
| Authors | Levin, GP, Robinson-Cohen, C, de Boer, IH, Houston, DK, Lohman, K, Liu, Y, Kritchevsky, SB, Cauley, JA, Tanaka, T, Ferrucci, L, Bandinelli, S, Patel, KV, Hagström, E, Michaëlsson, K, Melhus, H, Wang, T, Wolf, M, Psaty, BM, Siscovick, D, Kestenbaum, B |
| Journal | JAMA |
| Volume | 308 |
| Issue | 18 |
| Pagination | 1898-905 |
| Date Published | 2012 Nov 14 |
| ISSN | 1538-3598 |
| Keywords | 25-Hydroxyvitamin D3 1-alpha-Hydroxylase, Aged, Chronic Disease, Cohort Studies, Female, Genetic Variation, Genotype, Hip Fractures, Humans, Low Density Lipoprotein Receptor-Related Protein-2, Male, Meta-Analysis as Topic, Myocardial Infarction, Neoplasms, Polymorphism, Single Nucleotide, Receptors, Calcitriol, Receptors, Cell Surface, Risk, Steroid Hydroxylases, Vitamin D, Vitamin D3 24-Hydroxylase |
| Abstract | <p><b>CONTEXT: </b>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.</p><p><b>OBJECTIVE: </b>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.</p><p><b>DESIGN, SETTING, AND PARTICIPANTS: </b>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.</p><p><b>MAIN OUTCOME MEASURE: </b>Composite outcome of incident hip facture, myocardial infarction, cancer, and mortality over long-term follow-up.</p><p><b>RESULTS: </b>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.</p><p><b>CONCLUSION: </b>Known associations of low 25-hydroxyvitamin D with major health outcomes may vary according to common genetic differences in the vitamin D receptor.</p> |
| DOI | 10.1001/jama.2012.17304 |
| Alternate Journal | JAMA |
| PubMed ID | 23150009 |
| PubMed Central ID | PMC3645444 |
| Grant List | R01AG027002 / AG / NIA NIH HHS / United States N.1-AG-1-2111 / AG / NIA NIH HHS / United States N01 AG062101 / AG / NIA NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States R01-AG032098 / AG / NIA NIH HHS / United States R01 MD009164 / MD / NIMHD NIH HHS / United States HL096875 / HL / NHLBI NIH HHS / United States N01 HC015103 / HC / NHLBI NIH HHS / United States M01 RR000069 / RR / NCRR NIH HHS / United States 263 MD 821336 / MD / NIMHD NIH HHS / United States R01 AG029364 / AG / NIA NIH HHS / United States K01 AG030506 / AG / NIA NIH HHS / United States R01 HL087652 / HL / NHLBI NIH HHS / United States HL087652 / HL / NHLBI NIH HHS / United States N01 AG062106 / AG / NIA NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States N01-HC-85086 / HC / NHLBI NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States R01 HL105756 / HL / NHLBI NIH HHS / United States R01 AG032098 / AG / NIA NIH HHS / United States P30 DK063491 / DK / NIDDK NIH HHS / United States HHSN268200782096C / HG / NHGRI NIH HHS / United States / / Intramural NIH HHS / United States N01 HC-55222 / HC / NHLBI NIH HHS / United States HHSN268201200036C / HL / NHLBI NIH HHS / United States N01 AG062103 / AG / NIA NIH HHS / United States N.1-AG-1-1 / AG / NIA NIH HHS / United States M01RR00069 / RR / NCRR NIH HHS / United States N01-HC-75150 / HC / NHLBI NIH HHS / United States 263 MD9164 / MD / NIMHD NIH HHS / United States R01 HL084443 / HL / NHLBI NIH HHS / United States R01 AG027002 / AG / NIA NIH HHS / United States R01-AG029364 / AG / NIA NIH HHS / United States N01HC75150 / HL / NHLBI NIH HHS / United States DK063491 / DK / NIDDK NIH HHS / United States N01-HC-85079 / HC / NHLBI NIH HHS / United States HHSN268201200036C / / PHS HHS / United States HHSN268200782096C / / PHS HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States N01 HC045133 / HC / NHLBI NIH HHS / United States R01 HL096875 / HL / NHLBI NIH HHS / United States N01 HC035129 / HC / NHLBI NIH HHS / United States N01-AG-5-0002 / AG / NIA NIH HHS / United States P30 AG021332 / AG / NIA NIH HHS / United States |