Genetic variants and associations of 25-hydroxyvitamin D concentrations with major clinical outcomes.
Genetic variants and associations of 25-hydroxyvitamin D concentrations with major clinical outcomes.
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DOI：
10.1001/jama.2012.17304
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发表时间：
2012-11-14
影响因子：
120.7
通讯作者：
Kestenbaum, Bryan
中科院分区：
文献类型：
--
作者：
Levin, Gregory P.;Robinson-Cohen, Cassianne;de Boer, Ian H.;Houston, Denise K.;Lohman, Kurt;Liu, Yongmei;Kritchevsky, Stephen B.;Cauley, Jane A.;Tanaka, Toshiko;Ferrucci, Luigi;Bandinelli, Stefania;Patel, Kushang V.;Hagstrom, Emil;Michaelsson, Karl;Melhus, Hakan;Wang, Thomas;Wolf, Myles;Psaty, Bruce M.;Siscovick, David;Kestenbaum, Bryan
在基于社区的大型前瞻性研究中，较低的血清 25-羟基维生素 D 浓度与许多慢性疾病的较高风险相关。底物 25-羟基维生素 D 必须转化为 1,25-二羟基维生素 D 才能获得完整的生物活性，复杂的代谢途径表明，维生素 D 代谢的个体差异可能会改变所测血清 25-羟基维生素 D 的临床结果。旨在研究编码维生素 D 结合蛋白、巨蛋白、cubilin、CYP27B1、CYP24A1 和维生素 D 受体 (VDR) 的基因内的常见变异是否会改变低 25-羟基维生素 D 与主要临床结果的关联。对来自社区心血管健康研究的 1514 名白人参与者（从美国 4 个地区招募）的发现队列中的 141 个单核苷酸多态性进行检查。参与者在 1992 年至 1993 年期间进行了血清 25-羟基维生素 D 测量，并进行了平均 11 年的随访（截至 2006 年）。在独立的、以社区为基础的美国健康、老龄化和身体成分研究（n=922；随访：1998-1999 年至 2005 年）、意大利基安蒂 Invecchiare（n=835；随访：1998-2000 年至 2006 年）和瑞典乌普萨拉成年男性纵向研究（n=970；随访： 1991-1995 年至 2008 年）队列研究。长期随访中髋部骨折、心肌梗死、癌症和死亡率的综合结果。在发现阶段确定了 5 个单核苷酸多态性与低 25-羟基维生素 D 浓度之间的相互作用，其中 1 个涉及在独立荟萃分析中复制的 VDR 基因变异。在心血管健康研究参与者中，低 25-羟基维生素 D 浓度与复合结果风险比相关，对于 rs7968585 具有 1 个次要等位基因的患者，复合结果风险比为 1.40（95% CI，1.12–1.74）；对于 rs7968585 具有 2 个次要等位基因的患者，复合结果风险比为 1.82（95% CI，1.31–2.54）。相比之下，在该单核苷酸多态性具有 0 个次要等位基因的参与者中，没有证据表明存在关联（估计风险比为 0.93 [95% CI，0.70-1.24]）。已知的低 25-羟基维生素 D 与主要健康结果的关联可能因维生素 D 受体的常见遗传差异而异。
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. 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. 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. Composite outcome of incident hip facture, myocardial infarction, cancer, and mortality over long-term follow-up. 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. 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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4.1
作者：
Ji, Guang-Rong;Yao, Meng;Han, Zhu
通讯作者：
Han, Zhu
影响因子：
24
作者：
Kestenbaum, Bryan;Katz, Ronit;de Boer, Ian;Hoofnagle, Andy;Sarnak, Mark J.;Shlipak, Michael G.;Jenny, Nancy S.;Siscovick, David S.
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影响因子：
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作者：
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通讯作者：
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作者：
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通讯作者：
de Bakker, Paul I. W.
DOI：
10.1111/j.1532-5415.2000.tb03873.x
发表时间：
2000-12-01
影响因子：
6.3
作者：
Ferrucci, L;Bandinelli, S;Guralnik, JM
通讯作者：
Guralnik, JM