Association between polymorphic variation in VDR and RXRA and circulating levels of vitamin D metabolites.

Association between polymorphic variation in VDR and RXRA and circulating levels of vitamin D metabolites.
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DOI:
10.1016/j.jsbmb.2010.03.052
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发表时间:
2010-07
影响因子:
4.1
通讯作者:
Jacobs, E. T.
Jacobs, E. T.
中科院分区:
生物学2区
文献类型:
--
作者:
Hibler, E. A.;Jurutka, P. W.;Egan, J. B.;Hu, C.;LeRoy, E. C.;Martinez, M. E.;Thompson, P. A.;Jacobs, E. T.

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The vitamin D metabolite 1,25(OH)2D is the bioactive ligand of the vitamin D receptor (VDR). VDR forms a heterodimer with the retinoid X receptors (RXRs) that when bound to ligand influences the transcriptional control of genes that regulate circulating levels of vitamin D metabolites. Whether genetic variation in VDR or RXRA affects circulating levels of 1,25(OH)2D or 25(OH)D has not been established. We used a single nucleotide polymorphism (SNP) tagging approach to evaluate the association between SNPs in VDR and RXRA and serum levels of 1,25(OH)2D and 25(OH)D. A total of 42 tagSNPs in VDR and 32 in RXRA were analyzed in a sample of 415 participants. Principal components analyses revealed a gene-level association between RXRA and serum 1,25(OH)2D concentrations (P = 0.01), but not 25(OH)D. No gene-level association was found for VDR with either serum biomarker. At the single SNP level, a significant positive trend was observed for increasing 1,25(OH)2D levels with each additional copy of the A allele for RXRA SNP rs9409929 (Ptrend = 0.003). After a multiple comparisons adjustment, no individual SNP in VDR or RXRA was significantly associated with either outcome. These results demonstrate an association between genetic variation in RXRA and 1,25(OH)2D serum concentrations.
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