基因变异和25-氧维生素D度与主要临床结果的关联
Gregory P Levin1, Cassianne Robinson-Cohen, Ian H de Boer
1Department of Biostatistics, University of Washington, Seattle, USA.
JAMA
|November 15, 2012
概括
低维生素D水平会增加慢性疾病的风险,但维生素D受体 (VDR) 的遗传变异可以改变这种关联. 这项研究确定了一种特定的VDR基因变异,它修改了与低维生素D相关的健康风险.
科学领域:
- 遗传学和分子生物学
- 营养科学 营养科学
- 流行病学 流行病学
- 老年学是指老年学的学科.
背景情况:
- 血清25-基维生素D的低水平与各种慢性疾病的风险增加有关.
- 维生素D需要转化为其活性形式 (1,25-二基维生素D) 进行生物活性.
- 维生素D代谢的个体差异可能会影响测量维生素D水平的临床影响.
研究的目的:
- 确定关键维生素D路径基因中的常见遗传变异是否会改变低25-基维生素D和主要健康结果之间的关联.
- 研究的基因包括维生素D结合蛋白,巨氨酸,库比林,CYP27B1,CYP24A1和维生素D受体 (VDR) 的基因.
主要方法:
- 分析了来自心血管健康研究 (CHS) 的1514名白人参与者的141个单核酸多态 (SNPs).
- 测量了血清25-氧维生素D水平,参与者被跟踪了平均11年.
- 在三个独立的社区群体中进行了复制元分析:美国健康,衰老和身体组成,意大利Invecchiare in Chianti和瑞典乌普萨拉长度研究成年男性.
主要成果:
- 在发现阶段,五个SNP显示与低25-基维生素D的相互作用.
- 一个涉及维生素D受体 (VDR) 基因变异 (rs7968585) 的显著相互作用被复制.
- 在CHS参与者中,低25-基维生素D与复合结局 (关节骨折,心肌梗塞,癌症,死亡率) 的风险增加仅在具有1或2个小等位基因rss7968585的个体中相关;在没有零小等位基因的个体中没有观察到任何关联.
结论:
- 低血清25-基维生素D与主要健康结果之间的关联可能由常见的遗传变异来调节.
- 具体来说,维生素D受体 (VDR) 内的遗传差异会影响维生素D水平低的临床后果.
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