调节ORMDL3表达的基因变异有助于儿童喘的风险
Miriam F Moffatt1, Michael Kabesch, Liming Liang
1National Heart and Lung Institute, Imperial College, London SW3 6LY, UK.
Nature
|July 6, 2007
概括
遗传因素影响儿童喘. 全基因组关联研究确定了17q21染色体上的单核酸多态 (SNP),与儿童喘有很强的联系,特别是调节ORMDL3基因.
科学领域:
- 遗传学 是一个遗传学.
- 免疫学 免疫学 免疫学
- 儿科 儿科 儿科
背景情况:
- 儿童喘是由复杂的遗传和环境相互作用引起的.
- 对喘易感性的遗传基础仍然不完全理解.
- 全基因组关联研究 (GWAS) 对于识别遗传风险因素至关重要.
研究的目的:
- 系统地绘制单核酸多态 (SNPs) 对儿童发作的喘的影响.
- 为了确定与喘风险相关的特定遗传位置.
- 研究遗传变异和基因表达水平之间的关系.
主要方法:
- 全基因组关联研究 (GWAS) 分析了超过317,000个SNP.
- 利用基于家庭和病例的参考小组,包括994名喘患者和1243名对照人群.
- 德国和英国出生队列人群的独立复制研究.
- 在埃普斯坦-巴尔病毒 (EBV) 转变的淋巴状细胞细胞系中评估基因表达水平.
主要成果:
- 确定了染色体17q21标记物与儿童喘之间的强烈和可重现的关联 (P < 10(-12)).
- 复制研究证实了独立队列中的17q21位点关联 (P = 0.0003和P = 0.0005).
- 在17q21处的SNP与ORMDL3 (P<10(-22) 的转录水平显著相关,ORMDL3是编码内分泌网膜跨膜蛋白的基因.
结论:
- 调节ORMDL3表达的基因变异是儿童喘易感性的关键决定因素.
- 17q21位点代表了儿童喘的一个显著的遗传风险因素.
- 这项研究提供了基因变异,基因表达和喘病原体之间的分子联系.
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