维生素D不足的常见遗传决定因素:全基因组关联研究研究
Thomas J Wang1, Feng Zhang, J Brent Richards
1Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA. tjwang@partners.org
Lancet (London, England)
|June 15, 2010
概括
遗传变异显著影响维生素D水平,增加维生素D缺乏症的风险. 这项研究确定了影响大量欧洲人口维生素D状况的关键遗传位置.
科学领域:
- 人类遗传学 人类遗传学
- 营养生物化学 营养生物化学
- 分子流行病学分子流行病学
背景情况:
- 维生素D对骨健康至关重要,并在骨外组织中发挥作用.
- 循环中的25-基维生素D度受到阳光照射,饮食和遗传学的影响.
- 遗传因素被认为对维生素D的状况有很大影响,因为其具有很高的遗传性.
研究的目的:
- 为了确定与循环中的25-氧维生素D度相关的常见遗传变异.
- 调查发现的遗传变异与维生素D缺乏症风险之间的关系.
- 利用全基因组关联研究 (GWAS) 进行全面的遗传发现.
主要方法:
- 全基因组关联研究 (GWAS) 在15个队列中对33996名欧洲血统个体进行.
- 利用发现,in-silico复制和de-novo复制队伍进行可靠的验证.
- 使用各种测定方法 (放射性免疫测定,ELISA,质谱) 测量25-氧维生素D度,并确定不足值 (75nmol/L或50nmol/L).
- 采用Z分数加权的元分析,用于组合结果和确认变异的构造基因型得分.
主要成果:
- 在三个位点 (4p12在GC附近,11q12在DHCR7附近,11p15在CYP2R1附近) 确定了与25-基维生素D度相关的显著变异.
- 在聚合样本中,一个额外的位点 (20q13在CYP24A1附近) 达到全基因组显著性.
- 组合基因型得分最高四分之一的个体显著增加了维生素D缺乏症的风险 (OR为<75nmol/L的2.47,OR为<50nmol/L的1.92).
结论:
- 参与胆固醇合成,化和维生素D运输的基因附近的遗传变异影响维生素D状态.
- 这些已识别的基因位置对于了解维生素D代谢和状态至关重要.
- 这些位点的遗传变异有效地识别出具有较高维生素D缺乏风险的个体.
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